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Fava, 2007 The concept of recovery in major depression


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Psychiatry is faced with a dilemma: Once a patient is started on medication, when should such treatment end? Dr. Giovanni Fava and his associates Dr. Chiara Ruini and Dr. Carlotta Belaise propose a definition of recovery -- rather than remission -- and a psychologically supportive process to move patients to successful drug-free lives after 3 months of treatment with medication.


Psychol Med. 2007 Mar;37(3):307-17.

The concept of recovery in major depression.

Fava GA, Ruini C, Belaise C.


Abstract at http://www.ncbi.nlm.nih.gov/pubmed/17311684 A version of the full text is at http://www.psychiatrictimes.com/print/article/10168/1162992?printable=true ; selections below




There is increasing literature on the unsatisfactory degree of remission that current therapeutic strategies yield in unipolar depression. The aims of this review were to survey the available literature on residual symptoms of depression, to introduce new targets for therapy and to outline a more stringent definition of recovery.




Studies were identified by using MEDLINE (English language articles published from 1967 to June 2006; keywords: recovery, remission, residual symptoms, sequential treatment, drugs and psychotherapy, related to depressive disorder and depression) and a manual search of the literature and Index Medicus for the years 1960-2006.




Most patients report residual symptoms despite apparently successful treatment. Residual symptoms upon remission have a strong prognostic value. There appears to be a relationship between residual and prodromal symptomatology. The concept of recovery should involve psychological well-being.




Appraisal of subclinical symptomatology in depression has important implications for pathophysiological models of disease and relapse prevention. New therapeutic strategies for improving the level of remission, such as treatment on residual symptoms that progress to become prodromes of relapse, may yield more lasting benefits.



============== selections from http://www.psychiatrictimes.com/print/article/10168/1162992?printable=true ==============


The concept of recovery in major depression.


By Carlotta Belaise, PhD and Giovanni A. Fava, MD | June 1, 2008


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 longitudinal 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


Table 1




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.


Table 2



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.


It is hoped that more stringent criteria for recovery, endorsement of a longitudinal appraisal of affective disturbances, and more active involvement of the patient in the process of recovery may result in therapeutic efforts that yield more lasting relief.


Evidence-Based References

• Fava GA, Ruini C, Belaise C. The concept of recovery in major depression. Psychol Med. 2007;37:307-317.

• Fava GA, Ruini C, Rafanelli C. Sequential treatment of mood and anxiety disorders. J Clin Psychiatry. 2005;66:1392-1400.



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2. Fava GA, Kellner R. Staging: a neglected dimension in psychiatric classification. Acta Psychiatr Scand. 1993;87:225-230.


3. Fava GA. The concept of recovery in affective disorders. Psychother Psychosom. 1996;65:2-13.


4. Paykel ES. Achieving gains beyond response. Acta Psychiatr Scand Suppl. 2002;415:12-17.


5. Kupfer DJ. Achieving adequate outcomes in geriatric depression: standardized criteria for remission. J Clin Psychopharmacol. 2005;25 (suppl 1): S24-S28.


6. van Os J, Burns T, Cavallaro R, et al. Standardized remission criteria in schizophrenia. Acta Psychiatr Scand. 2006;113:91-95.


7. Falloon IR. Antipsychotic drugs: when and how to withdraw them? Psychother Psychosom. 2006;75:133-138.


8. Simpson HB, Huppert JD, Petkova E, et al. Response versus remission in obsessive-compulsive disorder. J Clin Psychiatry. 2006;67:269-276.


9. Paykel ES. Remission and residual symptomatology in major depression. Psychopathology. 1998;31:5-14.


10. Fava GA, Fabbri S, Sonino N. Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:1019-1027.


11. Boulenger JP. Residual symptoms of depression: clinical and theorhetical implications. Eur Psychiatry. 2004;19:209-213.


12. Paykel ES, Weissman MM. Social adjustment and depression. A longitudinal study. Arch Gen Psychiatry. 1973;28:659-664.


13. Judd LL, Akiskal HS, Zeller PJ, et al. Psychosocial disability during the long-term course of unipolar major depressive disorder. Arch Gen Psychiatry. 2000;57:375-380.


14. Nasser EH, Overholser JC. Recovery from major depression: the role of support from family, friends, and spiritual belief. Acta Psychiatr Scand. 2005;111:125-132.


15. Furukawa TA, Takenchi H, Hiroe T, et al. Symptomatic recovery and social functioning in major depression. Acta Psychiatr Scand. 2001;103: 257-261.


16. Paykel ES, Ramana R, Cooper Z, et al. Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995; 25:1171-1180.


17. Nelson JC, Portera L, Leon AC. Residual symptoms in depressed patients after treatment with fluoxetine or reboxetine. J Clin Psychiatry. 2005;66:1409-1414.


18. Simons AD, Murphy GE, Levine JL, Wetzel RD. Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year. Arch Gen Psychiatry. 1986;43:43-48.


19. Jarrett RB, Kraft D, Doyle J, et al. Preventing recurrent depression using cognitive therapy with and without a continuation phase: a randomized clinical trial. Arch Gen Psychiatry. 2001;58:381-388.


20. Bockting CL, Spinhoven P, Koeter MW, et al; Depression Evaluation Longitudinal Therapy Assessment Study Group. Prediction of recurrence in recurrent depression and the influence of consecutive episodes on vulnerability for depression: a 2-year prospective study. J Clin Psychiatry. 2006;67:747-755.


21. Fava GA, Grandi S, Zielezny M, et al. Cognitive behavioral treatment of residual symptoms in primary major depressive disorder. Am J Psychiatry. 1994;151:1295-1299.


22. Mahnert FA, Reicher H, Zalandek K, Zapotoczky HG. Prodromal and residual symptoms in recurrent depression. Eur Neuropsychopharmacol. 1997;7:158-159.


23. Fava GA, Grandi S, Canestrari R, Molnar G. Prodromal symptoms in primary major depressive disorder. J Affect Disord. 1990;19:149-152.


24. van Praag HM. About the centrality of mood lowering in mood disorders. Eur Neuropsychopharmacol. 1992;2:393-404.


25. Nystrom S, Lindegard B. Depression: predisposing factors. Acta Psychiatr Scand. 1975;51:77-87.


26. Murray LG, Blackburn IM. Personality differences in patients with depressive illness and anxiety neurosis. Acta Psychiatr Scand. 1974;50: 183-191.


27. Kennedy N, Paykel ES. Residual symptoms at remission from depression: impact on long-term outcome. J Affect Disord. 2004;80:135-144.


28. Fava GA, Ruini C, Belaise C. The concept of recovery in major depression. Psychol Med. 2007;37:307-317.


29. Trivedi MH, Rush AJ, Wisniewski SR, et al; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28-40.


30. Bartlett JA, Schleifer SJ, Johnson RL, Keller SE. Depression in inner city adolescents attending an adolescent medicine clinic. J Adolesc Health. 1991;12:316-318.


31. Keller MB. Past, present and future directions for defining optimal treatment outcome in depression: remission and beyond. JAMA. 2003; 289:3152-3160.


32. Fava M, Rush AJ. Current status of augmentation and combination treatments for major depressive disorder: a literature review and a proposal for a novel approach to improve practice. Psychother Psychosom. 2006;75:139-153.


33. Fava GA, Ruini C, Rafanelli C. Sequential treatment of mood and anxiety disorders. J Clin Psychiatry. 2005;66:1392-1400.


34. Otto MW, Smits JA, Reese HE. Combined psychotherapy and pharmacotherapy for mood and anxiety disorders in adults. Clin Psychol Sci Pract. 2005;12:72-86.


35. Hollon SD, Jarrett RB, Nierenberg AA, et al. Psychotherapy and medication in the treatment of adult and geriatric depression: which monotherapy or combined treatment? J Clin Psychiatry. 2005;66:455-468.


36. Fava GA, Rafanelli C, Grandi S, et al. Six-year outcome for cognitive behavioral treatment of residual symptoms in major depression. Am J Psychiatry. 1998;155:1443-1445.


37. Fava GA, Ruini C, Rafanelli C, et al. Six-year outcome of cognitive behavior therapy for prevention of recurrent depression. Am J Psychiatry. 2004;161:1872-1876.


38. Paykel ES, Scott J, Cornwall PL, et al. Duration of relapse prevention after cognitive therapy in residual depression: follow-up of controlled trial. Psychol Med. 2005;35:59-68.


39. Ma SH, Teasdale JD. Mindfulness-based cognitive therapy for depression: replication and exploration of differential relapse prevention effects. J Consul Clin Psychol. 2004;72:31-40.


40. Fava GA. Can long-term treatment with antidepressant drugs worsen the course of depression? J Clin Psychiatry. 2003;64:123-133.


41. Feinstein AR, Horwitz RI. Problems in the "evidence" of "evidence-based medicine." Am J Med. 1997;103:529-535.


42. Ryff CD, Singer B. Psychological well-being: meaning, measurement, and implications for psychotherapy research. Psychother Psychosom. 1996;65:14-23.


43. Zimmerman M, McGlinchey JB, Posternak MA, et al. How should remission from depression be defined? The depressed patient's perspective. Am J Psychiatry. 2006;163:148-150.


44. Jahoda M. Current Concepts of Positive Mental Health. New York: Basic Books; 1958.


45. Ryff CD. Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J Person Soc Psychol. 1989;57:1069-1081.


46. Fava GA, Ruini C. Development and characteristics of a well-being enhancing psychotherapeutic strategy: well-being therapy. J Behav Ther Exp Psychiatry. 2003;34:45-63.


47. Fava GA, Ruini C, Rafanelli C. Psychometric theory is an obstacle to the progress of clinical research. Psychother Psychosom. 2004;73:145-148.


48. Bech P. Modern psychometrics in clinimetrics: impact on clinical trials of antidepressants. Psychother Psychosom. 2004;73:134-138.


49. Faravelli C. Assessment of psychopathology. Psychother Psychosom. 2004;73:139-141.


50. Fava GA. The intellectual crisis of psychiatric research. Psychother Psychosom. 2006;75:202-208.


51. Tedlow J, Fava M, Uebelacker L, et al. Outcome definitions and predictors in depression. Psychother Psychosom. 1998;67:266-270.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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I didn't read the whole thing, but I like the concept of recovery much more than remission. As Alex has pointed out, the 12-step model of recovery has much to teach us in the psych meds w/d world. "Recovery" is also a much better fit for mental distress, in general. The whole "remission" construct is due to that age-old attempt to squeeze psychology / psychiatry into a bio-medical model.


But, I'll betcha that "recovery" eventually replaces "remission" even in the medical world. As we develop a more holistic approach to cancer, people will be said to be in recovery from cancer, as opposed to in remission from it. :)

1996-97 - Paxil x 9 months, tapered, suffered 8 months withdrawal but didn't know it was withdrawal, so...

1998-2001 - Zoloft, tapered, again unwittingly went into withdrawal, so...

2002-03 - Paxil x 20 months, developed severe headaches, so...

Sep 03 - May 05 - Paxil taper took 20 months, severe physical, moderate psychological symptoms

Sep 03 - Jun 05 - took Prozac to help with Paxil taper - not recommended

Jul 05 to date - post-taper, severe psychological, moderate physical symptoms, improving very slowly

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I believe the concept of "remission" in pharmapsychiatry is a justification for the continuation of medication indefinitely, in the expectation of relapse.


A paradigm shift to "recovery" would mean that patients can, indeed, learn and have acceptable quality of life without medication.


The core argument is whether depression is a chronic or episodic condition. Prior to pharmapsychiatry, it was considered episodic, with an excellent chance of recovery. A lot of it was situational. Pharmapsychiatry, as Bob Whitaker argues, converted an episodic condition into a chronic condition, and the high probability of recovery into high expectation of relapse.


Fava et al are striking at this core argument, demonstrating that their patients have, indeed, recovered without continuation of drugs.


As a concession to gain acceptability from medicine, they allow that medication may continue if needed.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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