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.

Reliability of personality disorder diagnosis during depression: the contribution of collateral informant reports.

OBJECTIVE: Research has found low concordance of personality disorder diagnoses made during depression versus after remission and made using patient versus collateral informants, but little is known about the reliability of personality disorder (PD) diagnoses made during depression using patient and collateral reports. METHOD: A total of 168 patients were evaluated for PDs during depression and following response using patient and close informant reports. kappa coefficients of inter-informant and test-retest reliability were calculated. RESULTS: After depression response, the proportion diagnosed with cluster A and C PDs fell by both patient and close informant report, and overall inter-informant reliability declined. Overall test-retest reliability did not differ between patients and informants. CONCLUSION: Collateral informants do not improve the reliability of PD diagnoses made during depressive episodes.

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.

Antecedent life events, social supports and response to antidepressants in depressed patients.

We evaluated 355 subjects who entered one of six double-blind placebo-controlled antidepressant drug trials with respect to the occurrence of antecedent adverse life events and their meaning to the patient. Patients were also assessed with regard to the degree of social support they received for the negative life event. The groups differed as to whether they did or did not meet the criteria for melancholic depression; 43 one-week placebo responders were statistically significantly more likely to believe that adverse life events predisposed them to depressive illness and that such life events precipitated their current depression, compared to 312 one-week placebo non-responders. Of the 312 patients who went on to the double-blind phase in which they were treated with either drug (n = 204) or placebo (n = 108), it was noted that, for both melancholic and non-melancholic patients, responders to drug treatment (but not placebo) had a more favourable ratio of social support received/social support desired than non-responders. Non-melancholic responders to both drug and placebo were statistically significantly more likely to report fewer adverse life events and have a less strong belief that adverse life events predispose one to depressive illness than non-responders. Melancholic patients did not show this trend.

Amphetamine and negative symptoms of schizophrenia.

The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n = 26) or placebo (n = 11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe.

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.

Patients' and informants' reports of personality traits during and after major depression.

The influence of major depression on patients' and informants' reports of personality traits was examined using the Structured Interview for DSM-III Personality Disorder, both before and after successful antidepressant or placebo treatment (N = 58). According to patients' reports, Cluster A and C traits decreased significantly from pre- to posttreatment, but Cluster B traits were unchanged, excluding an increase in histrionic traits. According to informants' reports, Cluster A and B traits did not change from pre- to posttreatment, but Cluster C traits decreased significantly after treatment, not including passive-aggressive traits. Moreover, informants generally reported much higher levels of maladaptive personality traits than patients themselves. These results suggest that informants should be used in future research on personality disorders until better assessment techniques are developed.

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.

Personality traits during depression and after clinical recovery.

We investigated whether and how acute depressive symptoms affect the self-report of maladaptive personality traits. Sixty-eight acutely depressed patients underwent the Structured Interview for DSM-III Personality Disorder (SIDP) before and after pharmacological treatment, allowing us to determine whether self-reported maladaptive personality traits are different during depression and after successful clinical recovery. After the initial SIDP administration (during an episode of major depression), patients received desipramine treatment (dose range 150-300 mg/day) over a course of 4-5 weeks before readministration of the SIDP. For those who recovered from their depression (n = 39), cluster III trait scores were significantly lower than those assessed at baseline, and there was a lower frequency of cluster III categorical diagnoses for a personality disorder after treatment than before treatment. Recovered patients also had significantly lower cluster I personality trait scores after treatment as compared with baseline ratings. For those who did not recover from their depression after treatment (n = 29), cluster I trait scores were in fact higher than those measured at baseline, but there were no differences in categorical diagnoses before and after treatment. Cluster II personality traits and categorical diagnoses were not different between those who did and did not recover from their depression. Thus, depression may have a significant effect on the assessment of cluster I and cluster III personality traits. It is possible that cluster I and III 'personality traits' may be interwoven with depressive features and therefore subject to state influences, whereas cluster II personality traits may entail enduring, long-term characteristic modes of thinking, feeling, and behaving.

Lithium prophylaxis of bipolar illness. The value of combination treatment.

Using a longitudinal life-table analysis, we assessed the efficacy of lithium alone, administered within the context of a naturalistic clinical setting, by calculating the probability of patients remaining free of an affective episode (manic or depressive) over a five-year course. In addition, for those who suffered a manic or depressive relapse, we attempted to analyse the subsequent course of patients who suffered a manic/hypomanic or depressive relapse and were then restabilised on lithium plus either a neuroleptic, carbamazepine, or a benzodiazepine, or lithium plus an antidepressant. Lithium alone offered an average 83% probability against an affective relapse after one year, 52% after three years, and 37% after five years. For patients who failed on lithium alone, it appeared that combination treatment offered greater protection against subsequent affective relapse than the initial course on lithium alone.

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.

Vitamin E in tardive dyskinesia: time course of effect after placebo substitution.

Alpha-tocopherol (vitamin E) has been found to be effective in the treatment of tardive dyskinesia (TD). Studies to date have been short in duration and have not found long-term carryover effects of vitamin E. The present study examined the persistence of the effects of vitamin E after longer term (36-week) treatment was discontinued. Vitamin E significantly improved TD over this period. However, the effects of vitamin E persisted so that TD scores approached baseline only after 12 weeks of placebo substitution.

A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis.

A group of 28 patients was treated to compare the effects on akathisia of the following: propranolol (80 mg/day), benztropine (6 mg/day), or placebo. Both propranolol and benztropine significantly improved akathisia by Day 3-5 of treatment. Placebo had no significant effects of akathisia. Three patients developed confusion or forgetfulness by Day 3 of benztropine treatment; these effects cleared upon discontinuation of benztropine.

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.

Sociotropy and autonomy: relationship to antidepressant drug treatment response and endogenous-nonendogenous dichotomy.

This study evaluated the relationship of sociotropic and autonomous personality traits with response to pharmacotherapy for 217 depressed outpatients using the Sociotropy-Autonomy Scale. Sociotropy was related to nonendogenous depression, whereas autonomy was related to endogenous depression. Subjects who had high autonomous-low sociotropic traits showed greater response to antidepressants (and greater drug-placebo differences) than those who had high sociotropic-low autonomous traits (who showed no drug-placebo differences). Hierarchical multiple regression analysis showed that the sociotropy-autonomy, but not the endogenous-nonendogenous, distinction was a predictor of drug treatment response. The combination of endogeneity and autonomy predicted response to placebo. If replicated, these findings may enable better matching of patient traits to various treatment modalities for depression.

Personality traits and response to desipramine.

We attempted to prospectively examine the effects of personality traits in 68 acutely depressed patients treated with desipramine over 4-5 weeks to assess whether the presence or absence of these traits played a role in response to antidepressant treatment. Overall the 39 responders had statistically significantly lower cluster III personality trait scores than non-responders, and a trend toward lower cluster I and cluster II scores. We then followed the 39 desipramine responders for up to 6 months on the dose to which they responded in accordance with standard clinical practice. Overall 23 of the 39 sustained their initial improvement, with eight relapsing and eight dropping out between 5 weeks and 6 months. When comparing these three groups with the 29 initial non-responders, those who sustained the 6-month response had statistically significantly lower cluster II, cluster III, and total personality scores than initial responders who relapsed, initial responders who dropped out and did not complete 6 months of treatment, and initial non-responders.

Depressive attributional style and the dexamethasone suppression test: relationship to the endogenous/melancholic distinction and to each other.

The dexamethasone suppression test (DST) and the depressive attributional style questionnaire (ASQ) were administered to 105 depressed patients prior to participation in a double-blind outpatient study and to 29 normal controls. The depressed patients were classified into three groups (1) met criteria for both research diagnostic criteria for definite endogenous depression and DSM III melancholia; (2) met criteria for neither, and (3) met criteria for one but not both. The group that met criteria for both RDC endogenous depression and DSM-III melancholia had a statistically greater frequency of abnormal DST versus the group that met neither criteria and the normal controls. With regard to ASQ, patients who met both criteria had statistically higher bad event internality scores but statistically lower bad event stability and globality scores as opposed to the group that met neither criteria. In general, normal controls had significantly lower bad event ASQ scores than the three depressive groups. There was no correlation between ASQ and DST, as both DST suppressors and nonsuppressors had similar ASQ scores and there was no correlation between ASQ bad event attributions and initial severity of depression.

Relationship of dose to antidepressant prophylactic efficacy.

We studied 75 patients on prophylactic antidepressants (imipramine or amitriptyline) to examine the effect of antidepressant dose on long-term prophylaxis of depression and to see whether lowering the dose during the prophylactic period affected subsequent relapse. There was no statistically significant difference in maintenance and prophylactic doses between the group that completed the 2 years free of a depressive episode, the group that had a depressive relapse and the group that dropped out of treatment before the end of the prophylactic period. However, the group that completed the 2 years free of a depressive episode had significantly less of a difference between the maintenance and prophylactic doses than the other 2 groups. Overall, 11/31 who remained on the same dose during the prophylactic period vs the maintenance period relapsed vs 17/25 who had their dose lowered during the prophylactic period vs the maintenance period. The difference was statistically significant.

Disappearance of memory deficits in outpatient depressives responding to imipramine.

We evaluated learning and memory in 50 depressed patients prior to and following 4 week treatment with imipramine compared to 21 normal controls tested at corresponding times. At baseline, the depressives did worse than normals on most memory tasks with the difficult memory tasks, regardless of store, modality or type of task best distinguishing between depressive and normal memory. Following imipramine treatment, responders performed better than nonresponders on the difficult memory tasks, and not significantly differently from controls on most tasks. This, as well as the fact that the responders improved to a greater degree than controls on most measures (in a few cases the difference was statistically significant) and the fact that at 4 weeks complete responders to imipramine did significantly better than partial responders to imipramine, indicates that relief from depression is highly related to improved memory functioning. The finding that complete responders to imipramine were not significantly worse than normal controls suggests that imipramine did not have significant adverse effects on memory.