Timothy I. Mueller

Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse.

BACKGROUND The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. METHODS MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N=82) and asymptomatic (N=155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs ( > 4 lifetime episodes) as a predictor of relapse/recurrence. RESULTS Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median=68 vs. 23 weeks) and to any depressive episode > 5 times faster (median=33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR=3.65) and was stronger than history of recurrent MDEs (OR=1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. LIMITATIONS Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. CONCLUSIONS MDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery.

RECOVERY, CHRONICITY, AND LEVELS OF PSYCHOPATHOLOGY IN MAJOR DEPRESSION

Major depression is a chronic and recurrent disorder for many people who are afflicted by it. There is a wealth of literature addressing the course of this disorder with follow-up times varying from several months to several decades, which gives a remarkably consistent picture in treated and untreated populations. Fortunately, most people who develop major depression recover from their initial episode; unfortunately, a significant minority do not recover fully and a near majority develop additional episodes. This article examines a selected group of studies that have examined the course of depression, with a focus on a large naturalistic longitudinal prospective study of affective disorders--the NIMH Collaborative Depression Study.

Cognitive–Behavioral Treatment for Depression in Alcoholism

Alcoholics with depressive symptoms score > or = 10 on the Beck Depression Inventory (A.T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) received 8 individual sessions of cognitive-behavioral treatment for depression (CBT-D, n = 19) or a relaxation training control (RTC; n = 16) plus standard alcohol treatment. CBT-D patients had greater reductions in somatic depressive symptoms and depressed and anxious mood than RTC patients during treatment. Patients receiving CBT-D had a greater percentage of days abstinent but not greater overall abstinence or fewer drinks per day during the first 3-month follow-up. However, between the 3- and 6-month follow-ups, CBT-D patients had significantly better alcohol use outcomes on total abstinence (47% vs. 13%), percent days abstinent (90.5% vs. 68.3%), and drinks per day (0.46 vs. 5.71). Theoretical and clinical implications of using CBT-D in alcohol treatment are discussed.

Bipolar I: a five-year prospective follow-up.

We explored the course of bipolar I illness in 172 probands who were followed up prospectively for up to 5 years. Probands were grouped into three categories based on whether the symptoms of the index episode were only depressed, only manic, or mixed/cycling. Data were available for recovery from the index episode, subsequent relapse, and rates of recovery from the first prospective episode. Pure manic probands had a significantly faster rate of recovery (median, 6 weeks) than the mixed/cycling probands (median, 17 weeks), and the pure depressive probands had an intermediate rate (median, 11 weeks). After 5 years of follow-up the mixed/cycling patients continue to have the lowest cumulative probability of recovery from the index episode. Mixed/cycling probands also had a substantially faster time to relapse after recovery from the index episode compared with pure manic patients. For those patients who relapsed, the mixed/cycling patients had the lowest cumulative probability of recovery from the first prospectively observed episode. The treatment received by these patients is described and there is a discussion of how this treatment may have influenced the findings on course and outcome.

Substance use disorder and posttraumatic stress disorder comorbidity: Addiction and psychiatric treatment rates.

This study compares substance use disorder (SUD) patients with and without a comorbid diagnosis of posttraumatic stress disorder (PTSD) on their use of addiction and psychiatric services over the 6-month period before an inpatient substance abuse admission. Compared with non-PTSD patients, PTSD patients had a greater number of hospital overnights for addiction treatment. Given no significant between-groups differences on any substance use indexes, PTSD patients apparently overuse costly inpatient addiction services. Despite their greater rates of psychiatric comorbidity, PTSD patients did not receive treatment for psychiatric problems at greater rates than did non-PTSD patients. Among PTSD patients, use of PTSD treatment was low. Assessment of psychiatric comorbidity and referral to treatment targeting co-occurring PTSD and other disorders are suggested as possible ways to reduce the high treatment costs associated with SUD-PTSD comorbidity.

Alcoholism and drug abuse in three groups — bipolar I, unipolars and their acquaintances

OBJECTIVE Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. METHOD Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. RESULTS The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. LIMITATION As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. CONCLUSIONS (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. CLINICAL IMPLICATIONS The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.

Bipolar I affective disorder: predictors of outcome after 15 years.

BACKGROUND Robust predictors of long-term outcome in bipolar affective disorder would have substantial importance to both clinicians and researchers. Such predictors are not available, however, perhaps because of the limitations of previous efforts to find them. METHODS In this study, 113 patients with bipolar affective disorder were followed semiannually for 5 years and annually for a subsequent 15 years. Of these, 23 (20.4%) had a poor long-term outcome indicated by the presence of mania or major depressive disorder throughout the 15th year. RESULTS Among the baseline demographic and clinical variables tested, only active alcoholism and low levels of optimum functioning in the preceding 5 years characterized poor outcome patients. The persistence of depressive symptoms in the first 2 years of follow-up predicted depressive symptoms 15 years later but the early persistence of manic symptoms seemed to have no predictive value. A regression analysis eliminated alcoholism as an independent predictor. Thus, only poor optimal functioning in the 5 years before baseline assessment, and the persistence of depressive symptoms in the two subsequent years, were independently associated with poor, long-term prognosis. LIMITATIONS Patients were recruited at tertiary care centers and sampling was therefore biased toward greater severity and chronicity. As is true of all naturalistic studies of course, treatment was not controlled. CONCLUSION These findings suggest the existence of a poor outcome, depression-prone subtype of bipolar affective disorder.

Manic-depressive (bipolar) disorder : the course in light of a prospective ten-year follow-up of 131 patients

For a five‐year period, 131 bipolar patients were followed every 6 months; for the next 5 years, they were followed yearly. Each patient was interviewed in a systematic way that gave information about episodes, hospitalizations, cycle lengths and the presence of alcoholism. Women and men were not significantly different in the number of follow‐up manic or depressive episodes or hospitalizations. Chronicity from index episode to the end of the 10‐year follow‐up was uncommon (4%). Alcoholism, which was common in these patients, showed a great diminution at the end of 10 years. Contrary to expectation, cycle lengths showed no systematic decrease in length over the follow‐up. In this naturalistic study, treatment intensity was not related to decreasing episodes or to changes in cycle length. The number of episodes in the first 5 years of follow‐up was not correlated with the number of episodes in the last 5 years. Cycle lengths in the first 5 years of follow‐up were similar in length to the last 5 years of follow‐up. A family history of mania in these bipolar patients was associated with more episodes in follow‐up than if such a family history were absent. The patients whose alcoholism predated the onset of their affective illness were less likely to have episodes in the follow‐up than the patients in whom affective illness predated the onset of the alcoholism.

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

BACKGROUND Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.

Five-year course of major depression: Effects of comorbid alcoholism

Some patients enter psychiatric treatment with clear cases of both major depression and alcoholism. While assumptions are often made about the relationships of these two conditions, little empirical evidence exists on the effects of sustained remissions in alcoholism on sustained remissions in depression. 127 patients with both disorders at treatment entry were studied over a 5-year period. Survival analyses with time-dependent covariates indicating alcoholism status were used to investigate remissions and relapses in major depression. Remission in alcoholism strongly and significantly increased the chances of remission in depression and were also related to reduced chances of depression relapse, although at a weaker level.