Partial remission, residual symptoms, and relapse in depression.

Partial remission from depression, with residual symptoms, is an important problem in depression. This paper reviews the frequency and features of this outcome, and its association with relapse. Residual symptoms occur in many depressed patients after acute treatment. They span the typical symptoms of depression, except those characteristic of severe disorders. Other persistent abnormalities include social dysfunction, dysfunctional attitudes, hypothalamic-pituitary-adrenal axis overactivity, shortened REM sleep latency, and mood lowering after tryptophan depletion. Associations of some of these with residual symptoms are not clear. There is growing evidence for similar residual symptoms in bipolar disorder, particularly bipolar depression. The most important consequence of residual symptoms is a much-increased risk of relapse, particularly in the first year. Residual symptoms are a strong indication for vigorous and longer than usual continuation of antidepressant treatment in order to prevent relapse. There is good evidence for the use of cognitive therapy as an adjunct.

Do treated psychiatric patients become later community cases? A prospective cohort study.

BACKGROUND: There have been few attempts to link two aspects of psychiatric epidemiology, severe disorder and milder 'common' mental disorder, by ascertaining whether subjects who have received psychiatric treatment for major disorders are identified later in epidemiological community surveys. METHODS: Subjects were from a national birth cohort study and had been followed prospectively from childhood to middle age, with concurrent information on treatment from psychiatric facilities. In two successive prevalence surveys of milder disorder at 36 and 43 years, the association between earlier treatment and being a later community case was examined RESULTS: Among 102 subjects who had been treated patients up to age 35 years, 52 (51%) were identified as definite community cases (36, 35%) or subthreshold cases (16, 16%) at either one or both later points. The proportion of community subjects who were previous psychiatric patients increased systematically from community non-cases, through subthreshold cases on one or both occasions, definite cases on one occasion, to definite cases on both occasions. CONCLUSIONS: About half of subjects who have received treatment from psychiatric facilities remain with persistent symptoms such as to identify them as definite or subthreshold cases of milder common mental disorder some years later.

Duration of relapse prevention after cognitive therapy in residual depression: follow-up of controlled trial.

BACKGROUND: Although there is good evidence that cognitive therapy (CBT) lessens relapse and recurrence in unipolar depression, the duration of this effect is not known. METHOD: One hundred and fifty-eight subjects, from a randomized controlled trial of CBT plus medication and clinical management versus medication and clinical management alone, were followed 6 years after randomization (4 1/2 years after completion of CBT) and the longitudinal course assessed. RESULTS: Effects in prevention of relapse and recurrence were found to persist, with weakening, and were not fully lost until 3 1/2 years after the end of CBT. Residual symptoms were also lessened. CONCLUSIONS: The effect of CBT in reduction of relapse and recurrence persists for several years. The potential value of subsequent additional CBT some time after cessation should be explored.

Long-term outcome of offspring after maternal severe puerperal disorder.

OBJECTIVE: To study adult mental health in offspring of mothers who experienced severe puerperal disorder. METHOD: Mothers, followed up a mean of 23 years after puerperal disorder requiring hospitalization, were interviewed regarding adult psychiatric illness, childhood neurotic symptoms and conduct problems of 48 offspring of the index episode and 62 additional siblings. RESULTS: In these predominantly young adults the lifetime rate of ICD-10 adult psychiatric illness was 26%, and was higher in offspring of puerperal episodes (35% vs. 15%, P = 0.07). There were also high rates of childhood symptoms and problems. CONCLUSION: There are high lifetime rates of adult psychiatric illness in young adult offspring of mothers with puerperal disorder, which are likely to increase further with time, and warrant special attention.

Treatment and response in refractory depression: results from a specialist affective disorders service.

BACKGROUND: The best treatment approaches for chronic severe refractory depression remain uncertain. This study aimed to identify short-term outcome and most successful somatic treatments of severe refractory depressives referred to an affective disorders service. METHODS: Patients with chronic refractory depression referred to a specialist affective disorders service over a 10-year period were studied. Using detailed case records of the index episode, courses of treatment and outcome were examined. RESULTS: Patients were predominantly middle-aged females with few prior episodes but long index episodes. Patients received higher antidepressant doses and more combinations on the specialist service. Very-high-dose antidepressants (tricyclics, velafaxine or tricyclic--MAOI combinations), usually augmented with lithium and often combined with ECT, were the most effective somatic treatments. Most subjects improved substantially, but few reached premorbid levels. LIMITATIONS: The study was retrospective. Treatment courses were sequential rather than random. CONCLUSIONS: Refractory depression is responsive to vigorous somatic therapy, although most patients continue with some symptoms.

Residual symptoms at remission from depression: impact on long-term outcome.

BACKGROUND: Although residual symptoms after remission from depression are common and predict early relapse, little is known about the impact of residual symptoms on longer-term clinical course of depression or social functioning. METHODS: Sixty severe recurrent depressives, who remitted from an index episode of depression with residual symptoms or below residual symptomatology, were followed-up at 8-10 years. Subjects underwent detailed longitudinal interviewing on course of depression, treatment and socioecomonic functioning over follow-up. RESULTS: Long-term follow-up data was obtained on all living subjects and 55 (95%) were interviewed. The residual symptoms group spent more time with depressive symptoms over follow-up but not at full criteria for major depression and showed greater impairment in longitudinal and follow-up social adjustment. No significant differences were found between the two groups in percentage recurring long-term, mean number of recurrences, readmissions, chronic episodes or clinical global outcome criteria. LIMITATIONS: Long-term clinical and social outcomes were assessed by a single retrospective longitudinal interview. CONCLUSIONS: Patients who remit from depression with residual symptomatology continue to have more depressive symptoms and impaired social functioning long-term and may need more aggressive treatment.

Outcome of postpartum disorders: a 10 year follow-up of hospital admissions.

OBJECTIVE: To determine readmission and recurrence rates of women admitted to psychiatric hospital with their babies, and index factors predicting subsequent course. METHOD: A total of 66 women were followed up after 10 years. Information was obtained from structured interviews or other personal contact, and from general practitioners and hospital notes. Psychiatric diagnoses were made according to Research Diagnostic Criteria (RDC). Outcome and predictive factors were investigated using survival analysis. RESULTS: A recurrence rate of 87.2%, and a readmission rate of 63.3% were found. Readmissions were more common after index schizophrenia than other diagnoses. The strongest predictor of readmission was previous psychiatric history. Among 27 subsequent pregnancies, puerperal recurrence was high among those with index psychoses (75-80%), but lower among those with index depression (27.3%). CONCLUSION: The recurrence rate is high, with a moderate readmission rate predicted by past psychiatric history. Continuing clinical vigilance over the long-term is required for these patients.

Life events and affective disorders.

OBJECTIVE: To summarize research in life events and affective disorders METHOD: Review of the literature. RESULTS AND CONCLUSION: Many studies have shown that episodes of unipolar depression are preceded by life events at higher rates than in control samples. A variety of stressful events are involved with only limited specificity but some relationship to social exit events. Life events also affect remission and relapse of depression. Effects of life events are less when the disorder has already been recurrent, particularly where illness is severe. Effects of life events are also weaker in bipolar disorder than unipolar, but major life events may be important in first onset. Recent evidence suggests a specific role of social rhythm disruption events in manic relapses. Causative chains are multifactorial and complex, and genetic factors can influence life event exposure.

Remission and recurrence of depression in the maintenance era: long-term outcome in a Cambridge cohort.

BACKGROUND: Long-term studies of severe depression have described high rates of non-recovery, recurrence, chronic incapacity and mortality. A more recent cohort was followed-up to ascertain whether the course had improved given developments in pharmacological and psychological treatments in the last 15 years. METHOD: Subjects from a cohort of 70 mainly severe recurrent depressives originally recruited to a shorter follow-up study from 1990-1992 were followed-up after 8-11 years. Data included longitudinal information on course of depression and other psychiatric disorders, pharmacological and psychological treatment and social functioning during follow-up. RESULTS: Sixty-nine (99%) subjects were successfully followed-up, with 61 of 66 living subjects interviewed and detailed follow-up data obtained in total on 65. Sixty (92%) of 65 subjects recovered during follow-up, with two-thirds subsequently suffering a recurrence. Eleven (17%) suffered from an episode of chronic depression of at least 2 years duration during follow-up. Social function at follow-up was good and there were high levels of pharmacological and psychological treatment. Greater severity of illness was the most consistent predictor of poor outcome. Times to recovery and recurrence and recovery and recurrence rates were very similar to older studies. CONCLUSIONS: The long-term outcome of depression still shows high recurrence rates and does not appear to have changed in the last 20 years.

Aftercare of depressed inpatients--service delivery and unmet needs.

BACKGROUND: In contrast to acute treatment, delivery of aftercare to depressed patients has not been well studied. Poor care may contribute to poor outcomes for treated depression. METHODS: One hundred and two patients discharged from hospital with unipolar depression were followed up 18 months later and were interviewed in detail regarding aftercare and treatment received. Unmet needs were assessed on the community version of the MRC Needs for Care Assessment. RESULTS: In the first month after discharge approximately 70 % of subjects received contacts with mental health services and in the first 3 months over 80 % received at least one contact. About 40 % were in contact with mental health services at 18 months. Needs assessment found comparatively low unmet needs, reaching highest levels (around 25 % in any 6-month period) for medication. Two-thirds of unmet needs for medication and psychotherapy were due to patient refusal or non-compliance. Aftercare levels were higher in those with more previous admissions and were unrelated to presence of personality disorder. CONCLUSIONS: There were some deficiencies in service aftercare for depressed patients in a British NHS setting, although unmet need was not high. Some aftercare failures reflect patient reluctance to receive further treatment, representing a challenge to overcome in patients entitled to autonomous choices.

Achieving gains beyond response.

OBJECTIVE: To review adverse outcomes following response in treatment of depression. METHOD: Review of published literature with particular emphasis on key papers. RESULTS: Moderately high rates of relapse and recurrence are found in naturalistic follow-up studies of depressed patients receiving modern treatment. These are reduced but not abolished in controlled trials by continuation and maintenance treatment with antidepressants. Suicide rates in follow-up studies are much elevated compared with the general population. Social function is impaired and remits more slowly than depressive symptoms. A key outcome is the occurrence of incomplete remission with residual symptoms, which is associated with high relapse rates and impaired social function. CONCLUSION: It is important to achieve complete remission in depression. Elimination of residual symptoms is an important target for full treatment of the depressive episode, in order to avoid later adverse outcomes.

Which depressions are related to life stress?

This paper examines the relationship of recent life events to specific kinds of depression using published studies and the author's own work. An overall effect of life events on depression has been found consistently and is moderate in degree. In suicide attempts there are stronger and more immediate effects than in depression. Life events precede both non-melancholic and melancholic depressions. It is only in recurrent depressions that life events are less common with melancholic pictures. Life events influence bipolar disorder as well as unipolar. Mania may be preceded by life events, particularly those involving social rhythm disruption, but it is harder to rule out events which are consequences of insidious development of illness. There are strong effects of life events and social support in postpartum depressions but in postpartum psychoses these effects are absent. Events precede depression comorbid with other disorders as well as pure depression. The course of depression is also influenced by life stress with less remission where negative events occur after onset and better outcome where earlier adverse events are neutralized. Relapse is related to immediately preceding life events. However, where depressions are both severe and recurrent life stress effects weaken and as the number of episodes increases preceding life events lessen. These findings suggest that some kinds of depression are more related to psychosocial causation and some are more biological in origin.

Decision-making in mania: a PET study.

Poor decision-making is often observed clinically in the manic syndrome. In normal volunteers, decision-making has been associated with activation in the ventral prefrontal cortex and the anterior cingulate gyrus. The aim of this study was to evaluate task-related activation in bipolar manic patients in these regions of the prefrontal cortex using PET. Six subjects with mania, 10 controls and six subjects with unipolar depression (an affective patient control group) were scanned using the bolus H(2)(15)O method while they were performing a decision-making task. Activations associated with the decision-making task were observed at two levels of difficulty. Task-related activation was increased in the manic patients compared with the control patients in the left dorsal anterior cingulate [Brodmann area (BA) 32] but decreased in the right frontal polar region (BA 10). In addition, controls showed greater task-related activation in the inferior frontal gyrus (BA 47) than manic patients. A positive correlation (r(s) = 0.88) between task-related activation in the anterior cingulate and increasing severity of manic symptoms was found. Depressed patients did not show significant task-related differences in activation compared with control subjects in the regions of interest. In conclusion, these patterns of activation point to abnormal task-related responses in specific frontal regions in manic patients. Moreover, they are consistent with neuropsychological observations in patients with lesions in the ventromedial prefrontal cortex, who show similar difficulties with decision-making and provide early evidence for context-specific neural correlates of mania.

Stability and change in milder psychiatric disorder over 7 years in a birth cohort.

BACKGROUND: Relatively little is known regarding stability or change over time in milder psychiatric disorder identified in epidemiological studies. METHODS: Data were analysed on 2890 subjects from the 1946 British birth cohort study. Psychiatric disorder was identified at age 36 years using the Present State Examination Index of Definition and 7 years later at age 43 using a symptom scale, employing a threshold to give identical 6% prevalence of disorder. Predictors were derived from recent social data and information collected earlier in childhood and younger adulthood. RESULTS: Over 7 years, there was considerable movement between case and non-case status. Only 1.7% of the sample satisfied case criteria at both points. Approximately two-thirds of cases at age 36 had fallen below case levels at age 43 and two-thirds of cases at age 43 were new cases. Most onsets and remissions were between definite case and non-case levels, rather than around the threshold. The strongest predictors of onset and remission were recent demographic, social and life stress variables, and earlier reported nervous disorder, with contributions from parental social background, and life history variables in adolescence. CONCLUSIONS: There is considerable change over 7 years in milder psychiatric disorder, with around two-thirds of it episodic or fluctuating and one-third chronic. Recent social variables are strong predictors of change or chronicity, with some lasting contributions from childhood social setting and earlier life history.

A family history study of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by unexplained, disabling fatigue and is associated with high rates of comorbid depression. While the aetiology is unknown, findings from recent twin surveys suggest that genetic factors may be relevant to prolonged fatigue states (> 1 month). To date, however, there has been no exploration of the role of familial/genetic factors in operationally defined CFS. The aims of the present study were: (i) to examine whether CFS is familial by comparing the rates of CFS in the first-degree relatives of CFS cases and medical control subjects; and (ii) to determine whether the high rate of comorbid depression in CFS is reflected in a greater familial loading for affective disorder. Twenty-five CFS cases and 36 medical control subjects were assessed for fatigue symptoms based on the Centre for Disease Control (CDC) criteria for CFS, and for lifetime psychiatric symptoms using the Schedule for Schizophrenia and Affective Disorders-Lifetime Version. Informant family history was obtained regarding first-degree relatives using the CDC criteria and the Family History Research Diagnostic Criteria. In addition, informant history was supplemented by sending a questionnaire to first-degree relatives. There were significantly higher rates of CFS in the relatives of CFS cases compared with the relatives of control subjects. The rate of depression in the CFS cases was similar to previous studies but did not appear to reflect a greater familial loading for depression when compared with control subjects. However, these analyses were complicated by higher than expected rates of depression in the control group. These findings suggest that familial factors are important in the aetiology of chronic fatigue syndrome.

Continuation and maintenance therapy in depression.

This paper reviews longer term treatment for unipolar depression. Antidepressant continuation for prevention of early relapse has been routine for many years. Recent evidence supports a longer period of 9 months to 1 year after remission. Antidepressants are also effective in maintenance treatment for recurrent depression, and are indicated where there is clear risk of further episodes. Antidepressant withdrawal after continuation and maintenance should always be gradual, over a minimum of 3 months and longer after longer maintenance periods, to avoid withdrawal symptoms or rebound relapse. Trials of interpersonal therapy in the prevention of recurrence show some benefit, but effects are weaker than those of drug and additional benefit in combination is limited. There is better evidence for effects of cognitive therapy in preventing relapse and an emerging indication for its addition to antidepressants, particularly where residual symptoms are present.

How does cognitive therapy prevent relapse in residual depression? Evidence from a controlled trial.

This study examined the cognitive mediation of relapse prevention by cognitive therapy (CT) in a trial of 158 patients with residual depression. Scores based on agreement with item content of 5 questionnaires of depression-related cognition provided no evidence for cognitive mediation. A measure of the form of response to those questionnaires, the number of times patients used extreme response categories ("totally agree" and "totally disagree"), showed significant and substantial prediction of relapse, differential response to CT. and conformity to mediational criteria. CT reduced relapse through reductions in absolutist, dichotomous thinking style. CT may prevent relapse by training patients to change the way that they process depression-related material rather than by changing belief in depressive thought content.

Decision-making cognition in mania and depression.

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition. METHODS: Medicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing 'bets' on each decision. RESULTS: Both patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions--an impairment that correlated with the severity of their illness. CONCLUSIONS: These findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Stress and affective disorders in humans.

A consistent body of findings published over 30 years shows raised rates of life events before onset of clinical unipolar depression. A range of threatening events is implicated, with only limited specificity, although a somewhat closer relationship to interpersonal losses. Social support both buffers effects of life events and its absence also has some independent stressful effects. Life stress also affects outcome. Effects extend across the age range, but are weaker or absent in recurrent disorder, particularly when this is severe or melancholic. They are also weaker in bipolar disorder, where social rhythm disruption may have a particular effect. The causative contribution of life stress is of moderate size overall but does not exclude many other factors. Causative chains are complex and life stress itself is not fully independent, because available social support is shaped by personal capacity to form relationships, and occurrence of life events has some genetic elements and is predicted by disturbance in childhood.