Quality of life in major depressive disorder before/after multiple steps of treatment and one-year follow-up.

OBJECTIVE: This study examines the impact of major depressive disorder (MDD) and its treatment on quality of life (QOL). METHOD: From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult MDD out-patients at entry/exit of each level of antidepressant treatments and after 12 months of entry to follow-up. QOL was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring 'within-normal' QOL (within 10% of Q-LES-Q community norms) and those with 'severely impaired' QOL (>2 SD below Q-LES-Q community norms) were analyzed. RESULTS: Before treatment, no more than 3% of MDD patients experienced 'within-normal' QOL. Following treatment, statistically significant improvements were detected; however, the proportion of patients achieving 'within-normal' QOL did not exceed 30%, with >50% of patients experiencing 'severely impaired' QOL. Although remitted patients had greater improvements compared with non-remitters, 32-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing 'within-normal' QOL show a statistically significant decrease in non-remitters. CONCLUSION: Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD.

Disorders of decision in affective disease: an effect of beta-adrenergic dysfunction?

We investigated response bias (defined as the decision rule subjects adopt when uncertain) in two experiments using a variant of Signal Detection Theory (SDT) with the discrimination measure d'L and the bias measure CL, under which it is possible to independently evaluate discrimination and response bias. In the first experiment, manics, depressed subjects, and matched psychiatrically normal controls were tested with a recognition memory task with easier and more difficult components before and after 1 month of appropriate pharmacological treatment. This experiment showed that abnormally conservative bias was characteristic of depression and liberal (yea-saying) bias was found in mania regardless of severity of illness; discrimination deficits were found only when symptoms were severe. After treatment, aspects of discrimination worsened in both hypomanic and depressed nonresponders whereas response bias remained unchanged in these patients. In both groups of responders, improvements in response bias were more dramatic than improvements in discrimination. In the second experiment, psychiatrically normal hypertensives were tested with a Sternberg short-term memory scanning task on and off treatment with the centrally active beta-blocker propranolol. This experiment showed that treatment with propranolol modeled the bias deficit of depression; that is, bias became more conservative. Both sets of results suggest that disorders of decision may be modulated by beta-adrenergic function.

Long-term treatment effects of vitamin E for tardive dyskinesia.

BACKGROUND: Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment. METHODS: To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo. RESULTS: Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score. CONCLUSIONS: The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo.

High thresholds for movement perception in schizophrenia may indicate abnormal extraneous noise levels of central vestibular activity.

A theoretical argument proposes that thresholds for visual perception of movement should be abnormally high in schizophrenia. This may reflect a central vestibular dysfunction, consisting of abnormally high levels of extraneous noise within the neural activity of the central vestibulo-cerebellar complex. Two experiments are reported with results that support the hypothesis. To some extent, the disorder may explain the smooth pursuit eye movement dysfunction in schizophrenia. Relations to the dopamine hypothesis in schizophrenia are discussed.

Neuroleptic augmentation with alprazolam: clinical effects and pharmacokinetic correlates.

Alprazolam added to stable doses of neuroleptics in nine schizophrenic patients was associated with a 20%-30% mean reduction in positive and negative symptoms, although clinical response was variable and in some patients particularly brisk. The authors examined the possibilities of a pharmacokinetic effect of alprazolam on neuroleptic plasma levels and of a clinical effect of alprazolam. The modest increase in mean neuroleptic plasma levels did not correlate with clinical change, but those patients with the highest alprazolam plasma levels tended to show more robust clinical responses.

The dexamethasone suppression test in depressed outpatients and normal control subjects.

In contrast to a recently published report by Amsterdam and associates, the authors noted a higher frequency of abnormal dexamethasone suppression test results in 88 outpatients with primary depression (particularly the endogenous subtype) than in 49 normal controls.

The dexamethasone suppression test as a monitor of clinical recovery.

To evaluate the dexamethasone suppression test (DST) as an aid in monitoring clinical recovery, the authors evaluated 127 outpatients with major depression who received the DST during depression and after clinical recovery. Although DST response varied among the 73 patients who met the Research Diagnostic Criteria for definite endogenous depression, their mean postdexamethasone plasma cortisol level was significantly higher during depression than after recovery. However, the DST's utility in monitoring long-term outcome was not great, as there was a high chance of remaining stable for 6 months after recovery regardless of cortisol value during depression or after recovery.

Lithium prophylaxis of depression in unipolar, bipolar II, and cyclothymic patients.

The authors assessed lithium's prophylactic effect against depression in unipolar (N = 43), bipolar II (N = 102), and cyclothymic (N = 69) patients using a longitudinal life-table analysis and calculated the probability of remaining free of a depressive episode. The probability of remaining free of one depressive episode after 2 years of taking lithium ranged from 42% to 55% for the bipolar II patients, 31% to 42% for the unipolar patients, and 26% to 36% for the cyclothymic patients. The average probability of suffering one depressive episode severe enough to require either pharmacologic intervention or hospitalization in a 2-year period was 51% for the bipolar II patients, 64% for the unipolar patients, and 69% for the cyclothymic patients.

Clonidine in neuroleptic-induced akathisia.

Six hospitalized patients with neuroleptic-induced akathisia were treated with clonidine under single-blind conditions. Akathisia and anxiety at maximum clonidine dose were significantly lower than at baseline, although it was difficult to differentiate specific therapeutic effects from sedation.

Melancholic/endogenous depression and response to somatic treatment and placebo.

OBJECTIVE: The authors' goals were to examine the effects of somatic treatment and placebo in patients with and without endogenous/melancholic depression. METHOD: Before entry into one of four trials of antidepressant drugs versus placebo, 231 patients were assessed as to whether they met Research Diagnostic Criteria for definite endogenous depression and/or DSM-III criteria for major depressive episode with melancholia. These patients were prospectively assessed for subsequent response to antidepressant treatment or placebo. Previous studies of the effect of endogenous/melancholic depression on treatment response were also reviewed. RESULTS: Of the 76 patients with DSM-III melancholia given active medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the 44 patients with melancholia given placebo had a complete or partial response. Of the 76 depressed patients without melancholia given active medication, 46 (61%) had a complete or partial response, and 15 (43%) of the 35 depressed patients without melancholia given placebo had a complete or partial response. Moderately depressed patients with DSM-III melancholia had a significantly better response to active medication than did severely depressed patients with melancholia and showed the greatest difference between response to active medication and response to placebo. The results of the review of previous studies of the effect of endogenous/melancholic depression on treatment response were mixed. CONCLUSIONS: Depressed patients with melancholia were not particularly different from depressed patients without melancholia in their responses to antidepressant medication but did differ from patients without melancholia in their responses to active medication versus placebo, particularly if their depression was moderate and not severe. This suggests that patients with DSM-III melancholia may be unresponsive to nonsomatic treatments.

Essential fatty acid supplementation in tardive dyskinesia.

Preclinical and clinical observations suggest that enhancement of prostaglandin activity inhibits catecholamine release and may have antidyskinetic effects. A double-blind therapeutic trial with prostaglandin precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia. No beneficial effects were seen.

Relationship between hypomania and personality disorders before and after successful treatment.

OBJECTIVE: To examine the effect of hypomanic states on maladaptive personality traits and personality disorders, the authors evaluated personality traits and disorders of patients during an episode of hypomania and after successful somatic treatment. METHOD: The authors used the Structured Interview for DSM-III Personality Disorders to study 66 outpatients who had a lifetime diagnosis of bipolar disorder and who met the minimum Research Diagnostic Criteria for hypomania. All patients had a knowledgeable informant separately undergo the Structured Interview for DSM-III Personality Disorders during the patient's hypomanic state. Outpatients who successfully recovered from the hypomanic episode (N = 47) and their informants were read-ministered the interview 4-8 weeks after the initial assessment. RESULTS: During the hypomanic state, informants generally reported higher levels of maladaptive personality traits among patients than patients themselves. For the patients who recovered successfully from the hypomanic episode, a reduction in all maladaptive personality traits except schizoid and dependent traits was reported by both patients and their informants; however, the decrease reported by patients generally was much greater than that reported by informants. In addition, schizoid traits actually increased after successful treatment according to patient reports but were unchanged according to informant reports. CONCLUSIONS: Hypomania may be associated with an exacerbation of maladaptive personality traits, which may be attenuated after successful treatment. Even with the attainment of euthymic mood, however, about 50% of the cohort had at least one personality disorder, which suggests that a high degree of comorbidity may exist between bipolar disorders and maladaptive personality traits or personality disorders.

Dysfunctional attitudes in depressed patients before and after clinical treatment and in normal control subjects.

To evaluate the role of maladaptive thinking patterns in depression, the authors administered the Dysfunctional Attitude Scale to 112 depressed patients before and after 3-6 weeks of treatment with antidepressants or placebo. Twenty-two normal subjects were also assessed twice. Depressed patients had a significantly higher initial mean score than control subjects, but during treatment their score significantly decreased, and the posttreatment score of those with complete recoveries was nearly as low as the control subjects' final score. The higher the initial dysfunctional attitude score the poorer the response to treatment. Patients with endogenous depression had significantly lower scores than nonendogenously depressed patients.

Vitamin E treatment of tardive dyskinesia.

OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia.

Platelet [3H]imipramine binding in affective disorders: trait versus state characteristics.

Platelet [3H]imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders.

Trazodone for antidepressant-associated insomnia.

OBJECTIVE: The authors investigated trazodone as a hypnotic for depressed patients who had persistent, exacerbated, or new insomnia while taking either fluoxetine or bupropion. METHOD: Seventeen depressed patients who had insomnia while taking fluoxetine or bupropion were given either trazodone or placebo in a double-blind crossover trial. Sleep was assessed by self-report with the Pittsburgh Sleep Quality Index and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory. RESULTS: Improvement with trazodone, but not with placebo, was shown by the total Pittsburgh index scores and Yale-New Haven inventory total sleep scores and by the Pittsburgh index measures of sleep duration and Yale-New Haven inventory measures of early morning awakening, and there was a trend toward improvement in the Yale-New Haven inventory item regarding middle of the night awakenings. Subjective sleep quality and sleep latency also showed a trend toward improvement, but the Pittsburgh index measures of sleep efficiency and disturbances and the Yale-New Haven inventory item regarding difficulty falling asleep were unaffected by trazodone. One patient dropped out because of excessive daytime sedation with trazodone, and another dropped out because of nonresponse to placebo. Of the completers, 67% experienced overall improvement in sleep with trazodone according to a priori criteria, whereas only 13% experienced improvement with placebo. CONCLUSIONS: Trazodone is an effective hypnotic for patients with antidepressant-associated insomnia.

Effects of verapamil on tardive dyskinesia and psychosis in schizophrenic patients.

Nine hospitalized schizophrenic patients with tardive dyskinesia were treated with the calcium-channel antagonist verapamil under single-blind conditions. The tardive dyskinesia and activation scores decreased, and the anxiety/depression scores increased. The changes were small but statistically significant.

Pattern analysis of antidepressant response to fluoxetine.

Seventy patients with unipolar major depressive disorder were treated with fluoxetine or placebo in a 6-week double-blind trial and were evaluated by changes in scores on the Hamilton Rating Scale for Depression (HAM-D) and the global improvement measure of the Clinical Global Impressions (CGI) scale. High correlations were found between the changes in HAM-D scores from baseline to endpoint and the final CGI improvement ratings. In patients with moderate depression (baseline HAM-D score of 20 or more), the differences in endpoint analysis between active treatment and placebo groups were significant. A persistent pattern of improvement was noted in 27% of those receiving fluoxetine but in none of those receiving placebo. Physician and patient evaluations as determined by the improvement measure of the CGI were closely correlated.

Brain glycine levels following lithium toxicity: case report.

A case is reported of a patient who died as a result of lithium toxicity. Brain lithium levels and changes in brain glycine levels are discussed.

Amphetamine response and relapse risk after depot neuroleptic discontinuation.

Twenty-five schizophrenic outpatient subjects in a depot neuroleptic discontinuation study received an amphetamine challenge approximately 6 weeks after their last dose. Only five of these showed greater than three-point increases in positive symptoms on the BPRS, and all five relapsed within 30 days of the challenge. The 20 with less than three-point increases in positive symptoms showed extremely variable stability, relapsing from 20- greater than 600 days after the challenge. Thus, increase in positive symptoms after amphetamine may identify a group at risk for rapid relapse after neuroleptic discontinuation, but lack of such a response gives little prognostic information.