The Concept of Recovery in Major Depression

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Original release date 06/08. Approved for CME credit through May 2009. Educational Objectives After reading this article, you will be familiar with: • The difference between recovery and remission in major depressive disorder. • How residual symptoms affect long-term outcomes. • The clinical implications of relapse and recurrence. • The reasons for the proposed changes in assessing recovery. Who will benefit from reading this article? Psychiatrists, primary care physicians, neurologists, nurse practitioners, and other health care professionals. Continuing medical education credit is available for most specialists. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing board. Dr Belaise is a research fellow in the Affective Disorders Program of the department of psychology at the University of Bologna in Italy. Dr Fava is professor of clinical psychology at the University of Bologna and clinical professor of psychiatry at the State University of New York at Buffalo. The authors report that they have no conflicts of interest concerning the subject matter of this article. In clinical medicine, the term recovery connotes the act of regaining or returning to a normal or usual state of health. However, there is lack of consensus about the use of this term (which may indicate both a process and a state), as well as of the related word remission, which indicates a temporary abatement of symptoms. Such ambiguities also affect the concepts of relapse (the return of a disease after its apparent cessation) and recurrence (the return of symptoms after a remission). In an attempt to overcome these flaws, Frank and associates1 proposed a set of definitions that they developed after a review of longitudinal studies of mood disorders. The development of these criteria helped decrease inconsistencies among research reports, yet it did not touch some key issues in the conceptualization of these terms. First, according to their definitions, recovery occurs when the number and severity of symptoms fall below the threshold used for defining onset. This subthreshold level of symptoms remains for a specified period. However, this state cannot be equated with being asymptomatic and provides room for a wide range of subclinical conditions. Second, the definition of remission parallels the traditional medical concept of convalescence, a transitional period of reintegration after illness. The trajectory of the process is thus an important additional dimension that requires a longitudi- nal consideration of the development of disorders, encompassing prodromal, acute, and residual symptoms.2 Finally, the distinction between recovery and full remission is made on temporal grounds only. Neither recovery nor full remission differentiate whether active treatment is associated, even though recovery implies that therapy may have been discontinued. A depressed patient who has recovered and is currently drug-free is thus equated with another patient who is receiving long-term, high-dose antidepressant treatment. The need to develop standardized criteria for remission has received increasing attention, in the study of mood disorders and other psychiatric illnesses, such as schizophrenia and obsessive-compulsive disorder.3-8 There is growing awareness of the importance of achieving full recovery, to avoid later adverse outcomes.4 After a review of the literature on residual symptoms as the most important target for full treatment of the depressive episode and a discussion of the clinical and theoretical implications of this topic, we will analyze the concept of recovery in unipolar major depressive disorder. Residual symptoms In the past decade, increased attention has been paid to the presence of residual symptoms after treatment of major depression.9-11 Residual social maladjustment in recovered depressed patients was reported by several investigators and was found to correlate with long-term outcome.12-15, Residual symptoms following drug treatment and psychotherapy in depressed patients have been correlated with poor long-term outcome.13,16-20 A strong relationship between prodromal and residual symptoms was also substantiated.21 This hypothesis achieved independent replication and is supported by several lines of evidence.22 The most frequently reported symptoms involved anxiety and irritability. These findings were consistent with previous studies on prodromal symptoms of depression, which overlapped with results concerned with interpersonal friction, irritability, and anxiety and underwent independent replication.9,12,23-27 Thus substantial residual symptoms appear to characterize patients whose depression responded to pharmacological or psychological therapies. Anxiety, irritability, and interpersonal friction, in addition to specific depressive symptoms, appear to be common residual symptoms. Clinical implications There has been increasing awareness of the frequency of relapse and recurrence in the long-term outcome of depression.28 Unfavorable outcome seems to parallel the presence of substantial residual symptoms in patients who are judged to be in remission and no longer in need of active treatment. Indeed, residual symptoms are probably the most consistent predictors of relapse. In the same vein, there is increasing awareness that current forms of treatment seem to be insufficient for many adults and adolescents with depression.29,30 Expanding the definition of remission thus appears to play a key role in yielding an optimal treatment outcome.4,31 There are 2 main strategies for going beyond current, unsatisfactory levels of remission. The first is provided by augmentation and combination treatments; the other, by sequential strategies (Table 1).32,33 The evidence that may support the first strategy is, at present, purely inferential, except for the combination of pharmacotherapy and psychotherapy.34,35 If residual symptoms are the rule after completion of drug or psychotherapeutic treatment and their presence has been correlated with poor outcome, residual symptoms on recovery may progress to become prodromal symptoms of relapse. Thus, treatment directed toward residual symptoms may yield long-term benefits.2 In line with this hypothesis, treatments that are administered in a sequential order (psychotherapy after pharmacotherapy, psychotherapy followed by pharmacotherapy, one drug treatment following another, and one psychotherapeutic treatment following another) may be more successful in increasing the spectrum of therapy and in eliminating residual symptoms.33 There is a substantial body of evidence that supports the use of cognitive-behavioral therapy (CBT) after successful pharmacotherapy for decreasing the likelihood of relapse during follow-up 21,36-39; in 3 of the studies, follow-up was up to 6 years.36-38 The rationale of this approach is to use CBT resources when they are most likely to make a unique and separate contribution to patient well-being and to achieve a more pervasive recovery. It has been suggested that the most effective drugs in treating acute depression may not be the most suitable for postacute or continuation treatment.10 A new proposal Appraisal of the literature on residual symptoms in major depression entails several conceptual implications. First, current basic pathophysiological models of pathogenesis in depression neglect intermediate phenomenological steps in the balance between health and disease. A prodromal phase can be described in most instances of depression, and only a few patients are completely asymptomatic after treatment.10 Similarly, drug mechanisms that may be operational in the initial phase of treatment can change during long-term treatment and according to the stages of illness.40 Second, standard treatment of depression seems to neglect a fundamental aspect of the disorder concerning residual symptoms. Monotherapy, for example, is likely to be insufficient in most cases. Different treatments are generally compared using the rate of response they yield instead of the amount of residual symptoms. A recent study on the amount of residual symptoms after treatment with fluoxetine or reboxetine is a valuable exception.17 Such assessment may lead to a reevaluation of tricyclic antidepressants.10 Optimal combinations of treatment strategies need to be devised. Third, randomized controlled trials are generally not intended to answer questions about the treatment of individual patients.41 Consequently, we should accept the possibility that a treatment may determine abatement of symptoms in some patients, leave substantial residual symptoms in others, yield an unsatisfactory response in others, and provide no benefit or even cause harm in a few. The types of residual symptoms vary widely from patient to patient and need to be assessed individually.33 Fourth, the concept of mental health should be expanded. Ryff and Singer42 remarked that historically, mental health research is dramatically weighted on the side of psychological dysfunction and that health is equated with the absence of illness rather than the presence of wellness. They suggest that the absence of well-being creates conditions of vulnerability to possible future adversities and that the route to recovery lies not exclusively in alleviating the negative but in engendering the positive. In a survey on factors identified by depressed outpatients as important in determining remission, the most frequently mentioned were features of positive mental health, such as optimism, self-confidence, and a return to the usual level of functioning as well as growth, integration, autonomy, perception of reality, and environmental mastery.43,44 Such criteria were refined and expanded in the multidimensional model of psychological well-being by Ryff,45 which was applied in a variety of clinical settings.46 The psychological dimensions may be instrumental in assessing both the process and the definition of recovery. Table 2 presents modified dimensions of psychological well-being based on the Ryff model. Fava and colleagues28 have recently suggested a new set of criteria for defining recovery that encompass psychological well-being. The fact that a patient no longer meets syndromal criteria is insufficient. Not all symptoms are equally important.47-49 For instance, persistence of depressed mood is different from lack of concentration in an improved depressed patient. Often, currently used scales for assessing treatment outcome, such as the Hamilton Rating Scale for Depression (HAM-D), are inadequate for assessing the wide spectrum of residual symptoms.10 As a result, reliance on a cut-off point of a rating scale such as the HAM-D for establishing recovery may be misleading. The current conceptual model is, in fact, psychometric: severity is determined by the number of symptoms only, without enough attention being paid to their intensity, quality, or interference with everyday life.50 This means that we can diagnose a major depressive disorder if the patient meets 5 of the specific symptoms even though the symptoms can be mild and functioning may not be impaired. On the other hand, this may not be the case in a patient who presents with symptoms such as depressed mood and hopelessness, severe anhedonia, and fatigue, all of which have a devastating impact on quality of life. Greater end-point severity appears to be related to greater baseline severity.51 Moreover, reference to well-being may be optional for defining remission, but it appears to be unavoidable for recovery. Frank and associates1 emphasized the connection between the declaration of recovery and the possibility that treatment can be discontinued or prolonged only for preventive purposes. The symptomatic state of patients who are drug-free could be equated, in this case, with that of patients who receive continuation therapy. As a result, while the proposed criteria for full remission are amenable to improvement and validation, those concerned with recovery seem to need a multidimensional redefinition that reflects the clinician's orientation and prognosis, aside from a symptomatic assessment.1 In addition, the role of the patient in engendering his or her recovery by appropriate lifestyle, and by behavioral and cognitive strategies should be emphasized. There is a large body of evidence- reviewed in this article and supported by the poor outcome of patients in long-term studies-that clinicians who treat patients with unipolar depression often have partial therapeutic targets, neglect residual symptoms, and equate therapeutic response with full remission. 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