One-year outcome with antidepressant--treatment of bipolar depression.

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.

Does a combination regimen of thyroxine (T4) and 3,5,3'-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial.

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.

Induction of mania and cycle acceleration in bipolar disorder: effect of different classes of antidepressant.

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.

Recollection memory deficits in patients with major depressive disorder predicted by past depressions but not current mood state or treatment status.

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.

Backward masking task performance in stable, euthymic out-patients with bipolar disorder.

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.

Examining the Saskatchewan health drug database for antidepressant use: the case of fluoxetine.

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.

Group cognitive behavioral therapy for bipolar disorder: a feasibility and effectiveness study.

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.

A review of psychosocial outcome in patients with bipolar disorder.

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.

Estimated prevalence of the seasonal subtype of major depression in a Canadian community sample.

OBJECTIVE: To examine estimates of lifetime prevalence of seasonal affective disorder (SAD) in Toronto, Ontario. METHOD: Random telephone numbers were generated for the city of Toronto, and 781 respondents completed a telephone interview. Trained nonphysician interviewers conducted all interviews, which involved structured questions for diagnosing major depression. Patterns of symptom change across seasons were evaluated to establish a diagnosis of SAD according to DSM-III-R criteria. RESULTS: Correcting for sex and age, the prevalence of SAD defined by DSM-III-R criteria was 2.9% (95% CI, 1.7% to 4.0%), and the overall lifetime prevalence of major depression in the sample was 26.4% (95% CI, 23.3% to 29.4%). Some subjects were contacted for a follow-up interview conducted in person; the positive predictive value for the diagnosis of major depression for the telephone interview was 100%, and the negative predictive value was 93%. CONCLUSIONS: The seasonal subtype of depression represents 11% of all subjects with major depression, suggesting that SAD is a significant public health concern. The telephone interview demonstrated adequate reliability, indicating that it is appropriate for epidemiological surveys of this nature.

Thyroid hormone levels and recurrence of major depression.

OBJECTIVE: The relationship between basal thyroid hormone levels and acute antidepressant response has been studied, but any relationship between basal thyroid hormone levels and long-term course of depressive illness has not been evaluated. METHOD: The authors used a Cox regression survival analysis to evaluate the relationship between life course of depressive illness and basal levels of thyroid hormones (triiodothyronine [T(3)], thyroxine [T(4)], and thyrotropin) in 75 outpatients with unipolar major depressive disorder. RESULTS: Time to recurrence of major depression was inversely related to T(3) levels but not to T(4) levels. CONCLUSIONS: These data may be of clinical interest in view of the fact that T(3) is used to augment antidepressant response.

Impaired distractor inhibition on a selective attention task in unmedicated, depressed subjects.

BACKGROUND: Impaired distractor inhibition may contribute to the selective attention deficits observed in depressed patients, but studies to date have not tested the distractor inhibition theory against the possibility that processes such as transient memory review processes may account for the observed deficits. A negative priming paradigm can dissociate inhibition from such a potentially confounding process called object review. The negative priming task also isolates features of the distractor such as colour and location for independent examination. METHOD: A computerized negative priming task was used in which colour, identification and location features of a stimulus and distractor were systematically manipulated across successive prime and probe trials. Thirty-two unmedicated subjects with DSM-IV diagnoses of non-psychotic unipolar depression were compared with 32 age, sex and IQ matched controls. RESULTS: Depressed subjects had reduced levels of negative priming for conditions where the colour feature of the stimulus was repeated across prime and probe trials but not when identity or location was the repeated feature. When both the colour and location feature were the repeated feature across trials, facilitation in response was apparent. CONCLUSIONS: The pattern of results supports studies that found reduced distractor inhibition in depressed subjects, and suggests that object review is intact in these subjects. Greater impairment in negative priming for colour versus location suggests that subjects may have greater impairment in the visual stream associated with processing colour features.

Effect of number of episodes on wellbeing and functioning of patients with bipolar disorder.

OBJECTIVE: To examine the relationship between number of episodes and inter-episode functioning in bipolar disorder. METHOD: Sixty-four euthymic subjects with bipolar affective disorder completed the Medical Outcomes Questionnaire Short Form and the Global Assessment of Functioning Scale. Goodness-of-fit models were used to define the relation between episode number and level of function. RESULTS: Non-linear logarithmic and power relations best described the association between number of episodes and outcome. Number of past depressions was a stronger determinant of outcome than past manias. CONCLUSION: Strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively if function is to be maintained, with particular attention given to minimizing episodes of depression.

Is self-criticism unique for depression? A comparison with social phobia.

BACKGROUND: This study further examined the diagnostic specificity of the self-critical personality dimension, as measured by the Depressive Experiences Questionnaire (DEQ; Blatt et al., 1976. The Depressive Experiences Questionnaire. Yale University Press, New Haven). METHODS: Patients with major depression (n=26) were compared to social phobia patients (n=32). RESULTS: Depressed patients scored significantly higher on the DEQ Self-Criticism dimension. However, when current level of depressed mood was controlled for, self-criticism was not a significant predictor of diagnostic status. Further, the level of DEQ self-criticism reported by patients with social phobia was almost three times greater than the level reported in an earlier diagnostic specificity study with panic disorder patients [Bagby et al., 1992. Diagnostic specificity of the dependent and self-critical personality dimensions in major depression. J. Affect. Disord. 26, 59-64]. LIMITATIONS: Only one measure of self-criticism was used in this study, and the research design was cross-sectional rather than prospective. CONCLUSIONS: Self-criticism is not unique to major depression, and this personality dimension may be implicated in other forms of psychopathology [Blatt, 1991. A cognitive morphology of psychopathology. J. Nerv. Ment. Dis. 179, 449-458]. Some cognitive features believed to play an important role in depression may also be salient in persons with social phobia.

Mexiletine in treatment-resistant bipolar disorder.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of mexiletine, a medication with antiarrhythmic, anticonvulsant and analgesic properties, in treatment-resistant bipolar disorder patients. METHODS: Twenty subjects with rapid-cycling bipolar disorder who had failed to respond or were intolerant to lithium, valproic acid and carbamazepine were entered into the 6-week, open label study. Subjects were followed on a weekly basis for dosing of mexiletine, blood levels, and completion of the Hamilton Depression Rating Scale (HAM-D) and the Manic State Rating Scale (MSRS). "Burden of Mood Symptoms" (BMS) was calculated by combining scores for the HAM-D and MSRS. RESULTS: Thirteen subjects (10 female, 3 male), mean age 41 years (S.D.=7.6), and mean duration of illness 20 years (S.D.=7.7) completed the study. The dose range of mexiletine was 200-1200 mg/day. Full response (>/=50% reduction in BMS) was seen in 46% of the subjects, and a partial response (25-49% reduction in BMS) in 15%. Of note, 5/5 subjects with a mixed or manic state demonstrated a full or partial response. LIMITATIONS: This study has an open label design, and a small number of subjects. CONCLUSIONS: Mexiletine may be effective and safe in patients with highly treatment-resistant, chronic bipolar disorder. Randomized, controlled trials are required to confirm the current results.

Double-blind comparison of addition of a second mood stabilizer versus an antidepressant to an initial mood stabilizer for treatment of patients with bipolar depression.

OBJECTIVE: This study's purpose was to clarify the appropriate treatment of bipolar depression by comparing the addition of an antidepressant versus a second mood stabilizer for inpatients being treated with lithium carbonate or divalproex sodium. METHOD: Twenty-seven patients were randomly assigned to groups that received double-blind treatment with paroxetine or a second mood stabilizer (lithium carbonate or divalproex sodium) for 6 weeks. RESULTS: Both groups showed significant improvement in depressive symptoms during the 6-week trial. There were significantly more noncompleters in the group being treated with the two mood stabilizers than in the group being treated with a mood stabilizer and paroxetine. CONCLUSIONS: Both treatments appeared to be effective; however, the addition of an antidepressant may have greater clinical utility in the treatment of bipolar depression.

Suicidal ideation in major depression: sex differences and impact of comorbid anxiety.

BACKGROUND: Being female and having comorbid anxiety are both thought to increase suicidality in patients with major depression. Whether these effects are independent or related to severity of depression is not known. METHOD: We conducted a retrospective review of 533 patients (190 men, 343 women) with major depression at the time of assessment. RESULTS: Suicidal ideation was present in 57.8% of all patients, and 43.2% of all patients had a lifetime anxiety disorder. Significantly more women than men experienced suicidal ideation, and both men and women with a lifetime anxiety disorder were more likely to be suicidal. Age and severity of depression did not account for these results. CONCLUSIONS: In patients with a current major depression, being female and having a lifetime anxiety disorder increase suicidality independently of one another and independently of severity of depression.

Gabapentin as an adjunctive treatment in bipolar disorder.

OBJECTIVE: To evaluate the efficacy of gabapentin as an adjunctive treatment for bipolar disorder in both depressed and manic phases. METHOD: Thirty seven patients with bipolar type I or II with or without a rapid cycling course were openly treated with gabapentin added to current treatment for up to six months. Mood symptoms were rated weekly for 12 weeks then monthly for 3 months utilizing the HamD and YMS. RESULTS: Participants experienced a significant reduction in both depressive and manic symptoms. CONCLUSIONS: These findings are consistent with others in establishing the efficacy of gabapentin in both phases of bipolar disorder. LIMITATIONS: Small sample size and the use of an open uncontrolled design limit interpretation of results.

Do depressed subjects who have failed both fluoxetine and a tricyclic antidepressant respond to the combination?

BACKGROUND: Recent evidence suggests that the combination of fluoxetine and desipramine may provide a rapid and effective treatment for depression. METHOD: The current study evaluated 13 subjects with DSM-III-R nonpsychotic major depression who had previously failed either desipramine or imipramine and who were currently unsuccessfully treated with fluoxetine. Desipramine or imipramine was added to fluoxetine and Hamilton Rating Scale for Depression (HAM-D) scores, Beck Depression Inventory (BDI) scores, and plasma tricyclic levels were monitored for 3 weeks. RESULTS: Of the 13 subjects, 7 (54%) had a greater than 40% decline in HAM-D scores and 4 of these (31%) had 50% or greater decline in HAM-D. At week 3, responders (767 +/- 282 nmol/L) had a significantly higher mean tricyclic level as compared with nonresponders (515 +/- 95 nmol/L, F = 25.1, p < .0001), and change in BDI scores was significantly correlated with tricyclic level (r = -0.60, p < .05). CONCLUSION: These findings suggest that in some subjects the positive clinical effect of combining fluoxetine and a tricyclic antidepressant may be related to the plasma levels of the tricyclic compound.