INTERVIEW: Toward full remission: improvement in functional outcomes in depression

School of Psychiatry
University of New South Wales and Black Dog Institute
Sydney, AUStRAlIA

Toward full remission: improvement in functional outcomes in depression

Interview with G. Parker, Australia

Remission has somewhat varying meanings and operational definitions to the patient, the clinician, and the researcher. In response to five questions put by the interviewer the author responds by offering a clinical perspective. Such a clinical approach weights the importance of diagnosis and a formulation—particularly in identifying the particular depressive subtype and likely causes—as both should shape, if not dictate, the prioritized treatment modality and management nuances. If remission does not occur, then revisiting the diagnosis and considering which factors may be inhibiting progress is the next logical step.

Medicographia. 2014;36:508-511 (see French abstract on page 511)

Which clinical symptoms are clinically useful to evaluate functional remission in patients?

When judging remission as a clinician, not as a researcher, I tend to favor constructs rather than individual symptoms. Inviting the patients to judge their overall level of mood improvement in percentage terms is a useful initial probe question that most patients readily understand. there are no firm markers but I would expect a patient who had recovered from depression to report being “100% better” without caveats or, when questioned further, to note only minimal issues (ignoring any medication side effects for the moment). A second broad construct is the patient’s level of impairment in getting to work, functioning at work, and/or in addressing daily tasks. I would expect those who have experienced a remission to nominate no distinctive impairment. A third construct is how the patient enters the consulting room and interacts with the clinician—and thus weights “signs” rather than symptoms. Patients whose depression has remitted are likely to present with light in their eyes, a spring in their step, and be more likely to ask how the doctor’s week is proceeding. In essence, “lighter” and able to see beyond their own depression.

If the patient reports full remission it is generally necessary to seek further clarification. the depressed individuals who state that their depression has gone and say “I have my life back” are usually reporting a complete remission. the patient who states “It’s a miracle… I’m no longer depressed at all… you are a magician doctor” could have moved beyond depression remission to a hypomanic state. Such patients should be screened for a medication-induced hypomanic episode or for a previously undeclared or unidentified bipolar disorder.

I then favor reviewing the depressive features nominated by the patient as most distinctive or distressing when they were initially assessed. this tends to be more useful than assessing all theoretical or manual-listed depressive symptoms and allows the status of all initially distinctive symptoms to be investigated. Moving from a global assessment where remission may be suggested to a review of specific symptoms may identify some symptoms as present—be they residual symptoms or medication side-effects—and both allow improvement to be quantified more finely and the need for any management changes.

Some depressive symptoms indicating less than full remission show some specificity to the depressive subtype. For example, those with melancholia are likely to report that, while improved, early morning anergia and diurnal variation are still present to some degree, and here the consequence of so identifying any residual symptoms is to consider the need for changes in medications or dose regimens.

How long does it take to achieve functional remission?

As long as a piece of string is the flip response that comes to mind. those who remit fully may report so responding in a day, while others report days to years. Different types of depression, as well as different treatments, influence the speed of response.

As recently reviewed,1 we view melancholia as a “biological” depressive “disease,” showing a low placebo response rate (in the order of 10%) and a preferential response to physical treatments compared with a psychotherapy. In clinical practice, I find broader-action medications (eg, tricyclics, monoamine oxidase inhibitors) to be more effective and with a faster remission onset than narrow-action medications such as selective serotonin reuptake inhibitors (SSRIs), which generally require weeks or, occasionally, months before they possibly induce remission of a melancholic depressive episode. the multiple available medication augmentation strategies (as reviewed by Narasimhan and Kannaday2) are generally positioned as relevant to major depression per se. By contrast, we position them as being specifically relevant only to the “biological” depressive conditions (ie, melancholic and psychotic depression). We have employed several antidepressant augmentation strategies in the last decade, including low-dose antipsychotics and psychostimulants, which can induce very rapid remissions often as rapid as several days or weeks. the likelihood of remission will be reduced and the time to remission extended for many melancholic depressive patients if (i) only a narrow- action antidepressant is prescribed, (ii) the patient has a previously undeclared or undetected bipolar disorder (with melancholic depressive episodes), or (iii) is a rapid metabolizer of medication—as generally indicated by the complete absence of side effects and a lack of clinical improvement.

The nonmelancholic depressive conditions are heterogeneous and include depressive disorders induced by stress (eg, reactive depression, situational depression) and/or by personality style. the “reactive” conditions are to some degree simply more severe forms of “normal depression” where the depressive state is either self-limiting or highly responsive to environmental factors and the skills of the therapist. It is well recognized that the “placebo response” rate in controlled antidepressant drug trials is in the order of 40% to 60%—for both those in the active drug and placebo groups. Such subjects include true placebo responders, but also those who experience a “spontaneous remission” and, of relevance here, those where a nondrug intervention (eg, counseling, psychotherapy) will have induced a remission by effectively negating or neutralizing the impact of the depression-inducing stressor, or by effecting recognized nonspecific therapeutic ingredients (eg, empathy, optimism) that can be substantive. Functional remission will be slower (or not achieved) if the depressogenic stressors are unable to be redressed, if the patient has substantive anxiety or a personality disorder, if a therapeutic alliance is difficult to establish, if medication adherence is poor, or again if the wrong treatment is adopted.

What are the therapeutic goals necessary to achieve optimal global functioning?

Therapists vary in their emphases on making a diagnosis and formulation versus giving prominence to the patient’s narrative or life story, though they should not be positioned as mutually exclusive. I view the former as a central first step in setting the target of achieving a remission in a depressed patient. A diagnosis allows the clinician to logically select the most appropriate treatment options, while a formulation (explaining why “this” individual has “this” type of depression at “this” particular time) allows the therapist to factor in predisposing and precipitating causes for redressing in the management plan. As observed by Kahneman,3 “to be a good diagnostician, a physician needs to acquire a large set of labels for diseases, each of which binds an idea of the illness and its symptoms, possible antecedents and causes, possible developments and consequences, and possible interventions to cure or mitigate the illness.” A “diagnosis” is also important to the patient, with Montgomery4 observing “Just having a diagnosis means that the rest of your life can start… to know the cause of disease is to have control… patients want to know what is wrong, if it is serious, how long it will last, whether it will alter their life plans.”

A valid diagnosis is distinctly more likely to promote remission as it will shape the choice of the most appropriate treatment modality and the way in which it should be applied, whether sequentially (eg, initially prioritizing the patient’s melancholic depression by medication and then addressing his/her alcoholism with a specific program) or pluralistically (eg, if multiple modalities are used such as antidepressant medication and psychotherapy, how are they best assembled and combined). Many authors (eg, Petersen5) have considered the evidence and articulated a rationale for combination pharmacotherapy and psychotherapy. thus, the initial priority in managing a depressed individual is to determine whether the condition is unipolar or bipolar, a melancholic or nonmelancholic depression, and the contributing etiological factors that will require specific attention. That priority should be reprioritized if a full remission is not achieved in a reasonable period.

Establishing a therapeutic alliance is a worthy objective but achieving it in managing some depressive conditions (eg, psychotic depression) may be impossible or compromised by the gravity of the patient’s mood state. While involving family members is generally a wise general strategy (albeit respecting confidentiality issues), this may be central when the therapeutic alliance is problematic.

After deriving a diagnosis and formulation I believe that the therapist should be open with the patient and indicate the logical management steps. In managing some clinical scenarios (eg, bipolar depression) a precise and logical initial plan may be difficult to derive. In such circumstances I recommend an optimistic general statement (eg, “I have no doubt that we can get your mood swings under control but I cannot guarantee whether the first, second, or even third medication will do the job, so we will review progress on a regular basis”). Such a communication should have three key components. Firstly, to offer hope at a realistic level so that, if there is no response to the first intervention, the practitioner does not lose his/her credibility. Secondly, to generally explicate a sequential model, with only one treatment component being changed at any one time (to evaluate impact unconfounded by multiple changes). thirdly, to keep in close contact with the patient— be it weekly, fortnightly or, in rare cases, daily.

If improvement to remission is not proceeding as expected, it is necessary to investigate why. For example, is the initial diagnosis incorrect and, as a consequence, is there a paradigm failure (ie, the treatment—drug or nondrug—is inappropriate for the condition)? Could there be a nondepressive primary diagnosis? (eg, Parkinson’s disease). Is the patient taking his/ her medication correctly or “forgetting” (another reason for involving family members)? Is the medication ineffective because the patient’s alcohol consumption is excessive? Do side effects (or their absence) indicate that the patient may be a slow or rapid metabolizer? Have medical factors (eg, hypothyroidism, sleep apnea) been ruled out, and should a brain scan be undertaken to exclude any cerebral factor (especially hyperintensities)? If medication is the dominant modality, are there other factors (eg, severe independent anxiety, major financial problems, personality disorder, and marital difficulties) that would benefit from counseling, psychotherapy, or practical assistance? If the patient is still failing to improve then seeking a second opinion can often be wise.

What properties are necessary for antidepressants to achieve optimal functional remission?

Most formal recommendations weight “an” antidepressant being prescribed at a sufficient dose and for a “suitable period,” and often recommend the maintenance therapy principle that “the dose that gets you well should be continued to keep you well.”

While in broad agreement, I have a few qualifications and additional points to offer. I do not regard all antidepressants as equally effective across differing depressive disorders. If using an antidepressant for a nonmelancholic disorder, a narrow action medication may be sufficient while, as noted earlier, a broader-action medication such as a tricyclic antidepressant— as well as augmentation strategies—may be necessary to bring a melancholic episode to remission.

I tend to commence the antidepressant at half the recommended starting dose in case the patient is a slow metabolizer, and build to the recommended dose in 1 to 2 weeks. While it is commonly stated that all antidepressants can take many weeks or months to work, the evidence challenges that mythology.6 In essence, if an antidepressant is likely to induce a remission then some evidence of improvement (ie, a reduction of 20% or more in the severity of mood symptoms) should be observed in the first 10 days. thus, if a patient with melancholia has not responded to an adequate dose after 2 to 3 weeks, I move to augmentation or to a different antidepressant rather than wait for any more extended a period. As noted earlier, factors that may impede or advance remission include identification of the depressive subtype and recognition that differing depressive conditions show quite differential responses to differing medications and nondrug strategies, and concurrent drug and alcohol use, drug metabolizing status and presence of certain organic conditions. Patients who employ a wellbeing plan (ie, incorporating exercise, anxiety reducing strategies, dietary control, and augmentation with fish oil) tend to be more likely to achieve functional remission, as do those who are open rather than feeling stigmatized about their condition. Other authors7 have overviewed and detailed nuances of such an “integrative approach” to management.

Which associated strategies are useful to achieve functional remission?

In most patients with a biological depression (ie, melancholic, psychotic, bipolar), medication alone (whether as monotherapy or in combination or with use of an augmenting strategy) may suffice, even when the patient may have major stressors in their life—whether causes or consequences of the depression. Such depressive conditions are associated with profound anergia and most patients will tend to stay in bed for extended periods while a significant minority with “atypical” hypersomnolence will sleep excessively. Encouraging such patients to get out of bed early and engage in exercise (despite their innate resistance) can be distinctly helpful. For those who are shift workers, stabilizing their work hours can be fundamental. Reducing the stress load associated with work or school can be of some assistance. Advising the patient’s relatives as to how to best offer support will not only be of some benefit to many patients, but may redress the propensity for some relatives to be critical or judgmental of the patient. Regular review by the clinician is important for monitoring progress, while the clinician should be directly and indirectly advancing hope—so that the patient learns over episodes the important mantra that “this too will pass.” Kurian et al8 have provided a useful and practical overview of medication-based strategies for targeting key residual symptoms. For those with a nonmelancholic depression, concomitant treatment strategies are often best crafted by examining possible episode determinants.

For example, if anxiety has predisposed or precipitated an episode, then anxiety-reducing strategies should be included in the management plan. Predisposing personality nuances may benefit from psychotherapy, while many of the stressors and collateral damage generated by the episode (eg, marital discord) should be addressed, often most readily by counseling. the therapeutic ingredients brought by the clinician to managing nonmelancholic depression may have a substantive impact, so choosing a caring, competent, and readily available managing clinician is fundamental.

It is useful to examine strategies nominated by patients who have done well in managing their depressive episodes, and I abstract the principal ones from accounts of several hundred patients.8 They included adopting personal philosophical approaches (eg, live one day at a time; accept that the black dog is not your fault; affirm yourself as a worthwhile person; find glimmers of hope and swim toward them; focus on and appreciate the simpler things in life; never be sorry for yourself), socializing (eg, find a support group or rely on a key friend), planning and structuring the days, having a “happy folder” to record positive moments, exercising, and introducing de-stressing strategies (eg, meditation, yoga, avoiding talk back radio, and abandoning deadlines for healing). Such “inside out” perspectives complement and enrich the “outside in” literature on advancing remission. ■

1. Parker G, Paterson A. Melancholia: definition and management. Curr Opin Psychiatry. 2014;27:1-6.
2. Narasimhan M, Kannaday M. treating depression and achieving remission. Asian J Psychiatry. 2010;3:163-168.
3. Kahneman D. Thinking, fast and slow. london, UK: Penguin; 2011.
4. Montgomery K. How doctors think. Oxford, UK: Oxford University Press; 2006.
5. Petersen t. Enhancing the efficacy of antidepressants with psychotherapy. J Psychopharmacol. 2006;20:19-28.
6. Stassen H, Delini-Stula A, Angst J. time course of improvement under antidepressant treatment: a survival analytic approach. Eur Neuropsychopharm. 1993; 3:127-136.
7. Chokka P. Can an integrative approach to the management of depression help patients achieve functional recovery? A review of current literature. Depress Anxiety. 2013;2:1-10.
8. Kurian B, Greer t, trivedi M. Strategies to enhance the therapeutic efficacy of antidepressants: targeting residual symptoms. Expert Rev Neurother. 2009;9:975-984.
9. Wigney t, Eyers K, Parker G. Journeys with the Black Dog: Inspirational Stories of bringing Depression to Heel. Sydney, Australia: Allen and Unwin; 2007.

Keywords: antidepressant; depression; functional outcome; remission; treatment