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ABSTRACT BACKGROUND: Despite increasing awareness of the extent and severity of cognitive deficits in major depressive disorder (MDD), trials of cognitive remediation have not been conducted. We conducted a 10-week course of cognitive remediation in patients with long-term MDD to probe whether deficits in four targeted cognitive domains, (i) memory, (ii) attention, (iii) executive functioning and (iv) psychomotor speed, could be improved by this intervention.MethodWe administered a computerized cognitive retraining package (PSSCogReHab) with demonstrated efficacy to 12 stable patients with recurrent MDD. Twelve matched patients with MDD and a group of healthy control participants were included for comparison; neither comparator group received the intervention that involved stimulation of cognitive functions through targeted, repetitive exercises in each domain. RESULTS: Patients who received cognitive training improved on a range of neuropsychological tests targeting attention, verbal learning and memory, psychomotor speed and executive function. This improvement exceeded that observed over the same time period in a group of matched comparisons. There was no change in depressive symptom scores over the course of the trial, thus improvement in cognitive performance occurred independent of other illness variables. CONCLUSIONS: These results provide preliminary evidence that improvement of cognitive functions through targeted, repetitive exercises is a viable method of cognitive remediation in patients with recurrent MDD. [ABSTRACT FROM AUTHOR]

This is a study of the metabolic and distal cardiovascular/cerebrovascular outcomes associated with the use of second-generation antipsychotics (SGAs) compared to antidepressants (ADs) in adults aged 18-65 years, based on data from Thomson Reuters MarketScan® Research Databases 2006-2010, a commercial U.S. claims database. Interventions included clinicians' choice treatment with SGAs (allowing any comedications) versus ADs (not allowing SGAs). The primary outcomes of interest were time to inpatient or outpatient claims for the following diagnoses within one year of SGA or AD discontinuation: hypertension, ischemic and hypertensive heart disease, cerebrovascular disease, diabetes mellitus, hyperlipidemia, and obesity. Secondary outcomes included the same diagnoses at last follow-up time point, i.e., not censoring observations at 365 days after SGA or AD discontinuation. Cox regression models, adjusted for age, gender, diagnosis of schizophrenia and mood disorders, and number of medical comorbidities, were run. Among 284,234 individuals, those within one year of exposure to SGAs versus ADs showed a higher risk of essential hypertension (adjusted hazard ratio, AHR=1.16, 95% CI: 1.12-1.21, p<0.0001), diabetes mellitus (AHR=1.43, CI: 1.33-1.53, p<0.0001), hypertensive heart disease (AHR=1.34, CI: 1.10-1.63, p<0.01), stroke (AHR=1.46, CI: 1.22-1.75, p<0.0001), coronary artery disease (AHR=1.17, CI: 1.05-1.30, p<0.01), and hyperlipidemia (AHR=1.12, CI: 1.07-1.17, p<0.0001). Unrestricted follow-up results were consistent with within one-year post-exposure results. Increased risk for stroke with SGAs has previously only been demonstrated in elderly patients, usually with dementia. This study documents, for the first time, a significantly increased risk for stroke and coronary artery disease in a non-elderly adult sample with SGA use. We also confirm a significant risk for adverse metabolic outcomes. These findings raise concerns about the longer-term safety of SGAs, given their widespread and chronic use., (© 2015 World Psychiatric Association.)

Objective: To discuss the approach to the isolated finding of an elevated thyrotropin (TSH) level on routine biochemical screening of a depressed patient., Method: A focused literature review as well as discussion of published clinical guidelines and the formulation of a rational clinical approach., Results: Screening for thyroid dysfunction is part of the routine assessment of the depressed patient. It is not uncommon for such patients to have an isolated elevation of TSH levels with nor laboratory or clinical features of thyroid disease. There is often misunderstanding about how to deal with this isolated laboratory finding which can lead to unnecessary investigation and treatment., Conclusions: A rational approach to evaluation and management of an isolated elevated TSH level is suggested.

Objectives: To perform a critical review of the literature on the mood and cognitive changes associated with subclinical hypothyroidism (SCH), with an emphasis on older adults. To evaluate these data against the Consensus Statement on the management of SCH from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society., Method: A comprehensive literature review., Results: Subclinical hypothyroidism may be associated with an increased risk of mood and cognitive dysfunction, although the strength of this association and the efficacy of replacement hormone therapy require further investigation., Conclusion: It remains unclear whether SCH leads to significant mood and cognitive impairments in most older patients. More research is required to determine the nature and extent of this association and whether thyroid hormone replacement therapy is appropriate and effective in treating SCH-associated neurobehavioral impairments., (Copyright © 2012 John Wiley & Sons, Ltd.)

There is a well-established relationship between alterations of various hormonal systems and psychiatric disorders, both in endocrine and psychiatric patients. This has led to clinical and research studies examining the efficacy of the different hormones for treatment of depression. These data will be reviewed with particular regard to the thyroid, gonadal, pineal, and adrenal cortex hormones. The data generally provide limited, but varying evidence for the antidepressant efficacy of these hormones.

Altered hippocampal volume, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and neuroticism have each been implicated in the etiology of psychiatric disorders, especially depression. However, the relationship between these variables is not well understood. Here, we determined the effects of the BDNF Val66met polymorphism on the five-factor personality dimensions (assessed using the NEO-FFI), trait depression (assessed with the DASS-21) in a cross-sectional cohort of 467 healthy volunteers. A large matched subset of this cohort was also assessed for grey matter volume of the hippocampus and contiguous temporal cortical regions using magnetic resonance imaging. In Met carriers, elevations in neuroticism and trait depression and stress were associated with lower mean hippocampal volume, but there were no such associations in Val homozygotes. Trait depression, in particular, was found to moderate the effects of BDNF genotypes on hippocampal volume. Met carriers with high trait depression showed a reduction in grey matter volume of the mean hippocampus compared with Val homozygotes. These findings suggest that even in otherwise healthy subjects, trait depression may contribute to the susceptibility of Met carriers to hippocampal grey matter loss., (2008 Wiley-Liss, Inc.)

Objective: There is a current argument in thyroidology about whether the normal range for basal thyrotropin (TSH) is too broad. Some groups suggest that a TSH of less than 2.5 mIU/L is a better cut-off for euthyroidism. Because major depression is associated with changes in thyroid hormone status and thyroid hormones may be an effective treatment for major depression, we examined whether TSH levels above or below 2.5 mIU/L were related to clinical variables or treatment outcome in euthyroid patients with major depression., Methods: Outpatients with major depression (n =166) were assigned to high-normal and low-normal TSH groups based on their basal TSH levels. The 2 groups were compared along clinical variables and treatment outcome., Results: The low-normal TSH group was significantly more depressed, as measured by Hamilton Depression Rating Scale scores, and had more anxiety symptoms and suicidal tendencies than the high-normal group. There was no difference in treatment response between the groups., Conclusions: A comparison of low-normal and high-normal basal TSH groups with major depression revealed significant differences in severity and symptoms of depression but no difference in treatment outcome. These data are preliminary and require replication in a larger sample.

A functional polymorphism of the brain-derived neurotrophic factor, BDNF Val66Met, is associated with risk for major depression alongside impairments in memory and selective attention. This study aims to identify the mediating neural mechanisms in links between BDNF and depression using highly heritable electroencephalographic (EEG) recordings. In 305 healthy subjects, BDNF Val66Met genotypes were compared in terms of trait depression, neural function (EEG during a resting state) and cognitive performance. The mediating effects of the EEG brain imaging endophenotypes were also examined using structural equation (path) modeling. A genotype-endophenotype-phenotype path model showed that Met homozygosity predicted elevated working memory commission errors and altered EEG activity; that is elevated relative theta and delta power coupled with reduced alpha power. In turn, reduced EEG alpha activity mediated the relationship between the Met/Met genotype and trait depression. These findings demonstrate the utility of an integrative endophenotype approach. They suggest that the BDNF Met/Met homozygote has a direct impact on memory systems, but impacts trait depression via the secondary effects of neural changes.

Background: Patients with mood disorders have higher rates of obesity than the general population. With respect to this, little is known regarding how patient look like prior to treatment or the rates of change., Objective: To identify changes in the rates of obesity in never-treated patients with mood disorder over 4 years of follow-up., Methods: Sixty-six never-treated patients with mood disorders were evaluated via clinical interview, symptom assessment and body mass index (BMI). Patients were followed 4 years. Population attributable risk (PAR%) was calculated., Results: Patients in underweight and normal weight groups fell by nearly 29%, with a corresponding increase in patients entering overweight and obese groups. Rates of PAR% increased to 16.0, a significant 5-point increase over baseline., Limitations: This study had a small sample size and the population was ethnically homogenous. BMI was used as a maker of weight and not waist circumference., Conclusions: Over 4 years there was a significant increase in BMI and the risk conferred by obesity. Shift from normal weight to overweight and obese is a significant risk for patients with a mood disorder and clinical programs should consider interventions that might ameliorate risk of this shift early in the course of the illness.

Thyroxine is the standard replacement therapy for patients with clinical hypothyroidism. However, there has been recent interest in examining the potential advantages of combined thyroxine and triiodothyronine treatment for the treatment of hypothyroidism. The authors review the nine studies to-date and conclude that the variability and limitations in study design make definitive and clinically useful recommendations difficult. They therefore conducted a metaanalysis of the nine controlled studies examining the impact of combined thyroxine-plus-triiodothyronine versus thyroxine alone, with measures of psychiatric symptoms as the primary outcome. Their analysis reveals no significant difference in treatment effect on psychiatric symptoms in the nine controlled studies to date.

Major depression is a chronic disorder with a high morbidity and mortality. Approved treatment for major depression at present includes monotherapy with antidepressants of different pharmacologic classes. There is increasingly widespread use of two other options: augmentation, the addition to an antidepressant of a second compound that is not an antidepressant when used alone; and combination, which is the use of two antidepressants concurrently to enhance or accelerate response. This review focuses on the data available to support these various augmentation and combination treatments.

Objective: To evaluate the relative benefits of the combination of lithium and triiodothyronine (T3) in augmentation of antidepressants, compared with either lithium or T3 alone., Methods: We performed a 2-week, randomized, double-blind, placebo-controlled pilot study of the addition of lithium compared with T3 compared with the combination of both in subjects with major depressive disorder who had not responded to an antidepressant., Results: All groups improved significantly over the 2 weeks of treatment, but there were no significant between-group differences., Conclusion: There may be no advantage to a combination of these augmenting agents, although we failed to show separation between active treatments and placebo.

Objective: To examine the risk of relapse into mania or depression with varying duration of antidepressant treatment in a cohort of 59 patients with bipolar disorder., Method: An open naturalistic evaluation using life charting methods of patients with 1 year follow-up, who responded to antidepressant treatment and who then less or more than 6 months of antidepressant treatment., Results: Patients who received more than 6 months of antidepressant treatment were less likely to relapse into depression at follow-up of 1 year. There was no difference in relapse rates for mania in the different antidepressant treatment duration groups. Gender and bipolar subtype did not significantly affect relapse rates for depression or mania., Conclusion: Our data, taken with other studies, suggest that the duration of optimal antidepressant treatment in bipolar disorder must be further evaluated., (Copyright 2005 Blackwell Munksgaard.)

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.

Substitution of T4 with T3 for T4 replacement in patients with hypothyroidism was undertaken using a randomized placebo controlled study design. Forty individuals were included who had depressive symptoms on stable doses of levothyroxine. Combined T4 plus T3 did not have a significantly different effect on mood and well-being scores than did T4 alone.

Background: There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive. This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospectively for an average of three years., Method: Detailed life-charting data were obtained from 138 patients with bipolar disorder. Mood states were characterized as euthymic, subsyndromal, minor or major affective episodes based on rigorously defined criteria. The amount of time spent in these mood states during follow-up was examined., Results: Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic. The remainder of the time was spent in varying severity of mood states. However, the majority of time was spent with minor and subsyndromal symptoms, both manic and depressive. Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal, minor and manic symptoms. There was no difference in time spent with depressive symptoms between the two groups., Conclusions: Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal. Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder.

Background: Many patients with bipolar disorder (BD) do not regain full function following an acute illness episode, but the extent to which this impairment is the result of persistent symptoms has not been well established. This study examined factors associated with persistent subsyndromal symptoms in a well characterized group of BD patients who were prospectively followed for an average of 3 years., Methods: Detailed life charting data from 138 patients with BD were reviewed. Patients were categorized into euthymic, subsyndromal or syndromal groups according to the clinical state during their most recent year of follow-up. The three groups were then examined with respect to comorbidity, function and treatment received., Results: Patients with subsyndromal symptoms had high rates of comorbid anxiety disorders, and were more likely to have increased rates of eating disorders as well. Patients with subsyndromal symptoms had lower global assessment of function (GAF) scores than euthymic patients, and had as many clinic contacts and medication trials as patients with full episodes of illness., Conclusions: Persistent subsyndromal symptoms in BD patients are associated with high rates of comorbidity that is important to recognize and treat in order to optimize mood and functioning.

Some hypothyroid patients receiving levothyroxine replacement therapy complain of depressive symptoms despite normal TSH measurements. It is not known whether adding T(3) can reverse such symptoms. We randomized 40 individuals with depressive symptoms who were taking a stable dose of levothyroxine for treatment of hypothyroidism (excluding those who underwent thyroidectomy or radioactive iodine ablation of the thyroid) to receive T(4) plus placebo or the combination of T(4) plus T(3) in a double-blind manner for 15 wk. Participants receiving combination therapy had their prestudy dose of T(4) dropped by 50%, and T(3) was started at a dose of 12.5 micro g, twice daily. T(4) and T(3) doses were adjusted to keep goal TSH concentrations within the normal range. Compared with the group taking T(4) alone, the group taking both T(4) plus T(3) did not report any improvement in self-rated mood and well-being scores that included all subscales of the Symptom Check-List-90, the Comprehensive Epidemiological Screen for Depression, and the Multiple Outcome Study (P > 0.05 for all indexes). In conclusion, the current data do not support the routine use of combined T(3) and T(4) therapy in hypothyroid patients with depressive symptoms.

Endocrine disorders are associated with significant psychiatric morbidity. Psychiatric symptoms may manifest as discreet psychiatric syndromes or, more commonly, with a heterogenous group of nonspecific symptoms. Research is needed to understand the relations between hormone excess or deficiency and alterations of mood, cognition, and perception. It is important for clinicians to carefully screen for psychiatric morbidity in patients who present with endocrine disorders. Moreover, patients who appear to present with primary psychiatric syndromes should be carefully evaluated by physical examination and biochemical screening when appropriate to exclude the presence of an underlying endocrine disorder.

Studies have examined hippocampal function and volume in depressed subjects, but none have systematically compared never-treated first-episode patients with those who have had multiple episodes. We sought to compare hippocampal function, as assessed by performance on hippocampal-dependent recollection memory tests, and hippocampal volumes, as measured in a 1.5-T magnetic resonance imager, in depressed subjects experiencing a postpubertal onset of depression. Twenty never-treated depressed subjects in a first episode of depression were compared with matched healthy control subjects. Seventeen depressed subjects with multiple past episodes of depression were also compared with matched healthy controls and to the first-episode patients. Both first- and multiple-episode depressed groups had hippocampal dysfunction apparent on several tests of recollection memory; only depressed subjects with multiple depressive episodes had hippocampal volume reductions. Curve-fitting analysis revealed a significant logarithmic association between illness duration and hippocampal volume. Reductions in hippocampal volume may not antedate illness onset, but volume may decrease at the greatest rate in the early years after illness onset.

Objectives: Few studies have examined the question of how personality features impact outcome in bipolar disorder (BD), though results from extant work and studies in major depressive disorder suggest that personality features are important in predicting outcome. The primary purpose of this paper was to examine the impact of DSM-IV personality disorder symptoms on long-term clinical outcome in BD., Methods: The study used a 'life-charting' approach in which 87 BD patients were followed regularly and treated according to published guidelines. Outcome was determined by examining symptoms over the most recent year of follow-up and personality symptoms were assessed with the Structured Clinical Interview for DSM-IV (SCID-II) instrument at entry into the life-charting study., Results: Patients with better outcomes had fewer personality disorder symptoms in seven out of 10 disorder categories and Cluster A personality disorder symptoms best distinguished euthymic and symptomatic patients., Conclusions: These results raise important questions about the mechanisms linking personality pathology and outcome in BD, and argue that conceptual models concerning personality pathology and BD need to be further developed. Treatment implications of our results, such as need for psychosocial interventions and treatment algorithms, are also described.

Objective: The treatment of bipolar depression is a significant clinical problem that remains understudied. The role for antidepressant (AD) agents vs. mood stabilizers has been particularly problematic to ascertain., Method: Detailed life charting data from 42 patients with 67 depressive episodes were reviewed. Response rates and rates of switch into mania were compared based on the preceding mood state and on whether an AD or mood stabilizing (MS) agent was added following onset of depression., Results: Patients who became depressed following a period of euthymia were more likely to respond to treatment (62.5%) than patients who became depressed following a period of mania or hypomania (27.9%). The ratio of response to switch for previously euthymic patients was particularly favorable., Conclusion: Mood state prior to onset of depression in bipolar disorder appears to be an important clinical variable that may guide both choice of treatment administered and expectation of outcome to treatment.

Objective: To assess the effect of different antidepressants on induction of mania and cycle acceleration, commonly accepted unwanted effects of antidepressant treatment for acute bipolar depression. There is, however, the suggestion that certain classes of antidepressants may be less likely than others to cause these unwanted effects., Method: We conducted a prospective, open, naturalistic, life charting study to assess the occurrence of onset of mania and cycle acceleration attributable to two antidepressant classes: selective serotonin reuptake inhibitors (SSRIs) and bupropion., Results: No difference was found between the two drug classes for either antidepressant-induced mania or cycle acceleration. Antidepressant-induced mania was much more likely to occur in bipolar I rather than bipolar II patients. The overall occurrence of induction of mania and cycle acceleration was low across antidepressant classes., Conclusion: These findings suggest that there is probably no difference in the risk of antidepressant-induced mania or cycle acceleration across commonly used classes of antidepressants for the treatment of bipolar depression.

Background: Neuropsychological studies have suggested that memory systems reliant on medial temporal lobe structures are impaired in patients with depression. There is less data regarding whether this impairment is specific to recollection memory systems, and whether clinical features predict impairment. This study sought to address these issues., Method: A computerized process-dissociation memory task was utilized to dissociate recollection and habit memory in 40 patients with past or current major depression and 40 age, sex and IQ matched non-psychiatric control subjects. The Cognitive Failures Questionnaire was used to assess patients' perceptions of day-to-day memory failures., Results: Patients had impaired recollection memory (t = 4.7, P < 0.001), but no impairment in habit memory when compared to controls. Recollection memory performance was not predicted by indices of current mood state, but was predicted by self-assessments of impairment (beta = -0.33; P = 0.008) and past number of depressions (beta = -0.41; P = 0.001). There was no evidence that standard therapy with antidepressant medication either improved or worsened memory performance., Conclusions: The results confirm that patients with multiple past depressions have reduced function on recollection memory tasks, but not on habit memory performance. The memory deficits were independent of current mood state but related to past course of illness and significant enough that patients detected impairment in day-to-day memory function.

Background: Several studies have suggested that visual backward masking (VBM) impairment is present in patients with bipolar disorder, but the clinical features, such as current symptoms, treatment status and past burden of illness that may contribute to the impairment have not been well described. This study examined well-characterized euthymic patients on two VBM tasks to ascertain the extent of VBM impairment in this group and the clinical correlates of this impairment., Method: Twenty-eight euthymic patients with a DSM-IV diagnosis of bipolar disorder were matched by age, sex and IQ with 28 non-psychiatric control subjects. Both groups completed two VBM tasks; one required subjects to locate the target stimulus, one required identification of the target stimulus. Reaction times and error rates across a range of target-mask inter-stimulus intervals were assessed., Results: Patients were significantly slower and had more errors on both VBM tasks. There was a significant relation between reaction times on the identification task and past burden of illness, particularly past number of depressions. There was no discernible impact of treatment status on reaction time or performance, including no difference in lithium-treated versus not treated subjects., Conclusions: These results are consistent with previous reports of neuropsychological deficits in euthymic bipolar disorder patients. The potential benefit to employing tasks such as VBM is that it may provide a method for relating clinical variables such as illness burden with known neural pathways in order to elucidate better the pathophysiology leading to impaired cognitive performance in patients with bipolar disorder.

Objective: To examine the use of fluoxetine in an adult population in Saskatchewan., Methods: All adults in the Saskatchewan health care databases who had begun fluoxetine therapy between January 1992 and June 1996 and had not received an antidepressant in the six months before the index fluoxetine prescription were identified. Fluoxetine use for the subsequent six-month period was examined. The rates of completion of six months of fluoxetine, rates of stopping, switching to another serotonin-selective reuptake inhibitor (SSRI) or other class of antidepressant, resumption of fluoxetine, as well as average dosages taken and mean duration of therapy were determined. Rates were summarized as means with standard deviation., Results: Data were obtained for 11,322 subjects, of whom 68.2% were women; 17.4% were 65 years of age or older. The average prescribed daily dose of fluoxetine was 22.5 mg (SD=21.7) and the average duration was 88.1 days (SD=57.2). Only 18.9% of patients filled prescriptions for six months, 7049 (62.3%) stopped fluoxetine at least once for one month or more, and 17.3% were titrated to a higher dose, on average 71 days (SD=44) after the initiation of fluoxetine. The proportion of patients switching to another antidepressant was 13.6% (3.3% to another SSRI, 10.3% to other classes), after a mean of 69 days (SD=51) of fluoxetine treatment., Conclusions: The authors' data suggest that there is a potential underutilization of fluoxetine in the study population. Further research may be warranted to determine the proportion of depressed patients in this population and to better understand the stop-switch-resume pattern of antidepressant use.

Background: Bipolar disorder (BD) is a common disorder that results in significant psychosocial impairment, including diminished quality of life and functioning, despite aggressive pharmacotherapy. Psychosocial interventions that target functional factors could be beneficial for this population, and we hypothesized that the addition of group cognitive behavioral therapy (CBT) to maintenance pharmacotherapy would improve functioning and quality of life., Methods: Patients diagnosed (by SCID) with bipolar disorder attending an outpatient clinic of a mood disorders program participated in the study. All patients were on maintenance mood stabilizers, and were required to have controlled symptoms before entering the study. Mood symptoms were assessed with the Hamilton Depression Rating scale and Young Mania scale at baseline and 14 weeks. Objective and subjective functioning was rated at the same interval using the Global Assessment of Functioning scale and the Medical Outcomes Survey SF-36. Treatment was provided via a specific manual based on CBT principles that could be applied to this population., Results: Forty nine patients participated in this open trial, and 38 patients completed treatment. Objective and subjective indices of impairment showed improvement after 14 weeks. Both GAF and MOS scores increased significantly by the end of treatment., Limitations: This study was an open trial, and lack of control groups limits the interpretation of results. Because the study concerned effectiveness, the results do not clarify whether the improvement represents the normal course of illness or whether it is the result of the CBT intervention., Conclusions: The addition of group CBT to standard pharmacological treatment was acceptable to patients, and nearly 80% of patients complied with treatment. Despite the fact that mood symptoms were controlled at entry into the study, psychosocial functioning increased significantly at the end of treatment. Adjunctive CBT should be further investigated in this population.

Objective: The aim of this paper is to review outcome in patients with bipolar disorder as assessed by interepisode level of functioning, as until recently this dimension of outcome has been relatively under-emphasized., Method: Studies that examined psychosocial outcome in bipolar disorder were reviewed on the basis of rating measurements employed, length of follow-up, number of subjects followed and degree of impairment reported. Studies were included only if results from patients with bipolar and unipolar disorder were reported in such a way that the groups could be distinguished., Results: When studies of psychosocial outcome in bipolar disorder are examined in aggregate, it appears that 30-60% of individuals with this disorder fail to regain full functioning in occupational and social domains., Conclusion: This review highlights the fact that inter-episode functional recovery is incomplete in some patients, suggesting that comprehensive rehabilitative assessment and intervention may be essential to reduce the morbidity associated with this disorder.