Depression as a Chronic Disease: Issues in Maintenance Therapy and Long-term Management
Perry Dickinson, MD
University of Colorado
Department of Family Medicine
Copyright by the MacArthur Foundation

LECTURE OUTLINE
Background
Variations in clinical course
Risk factors for chronic course
Change points in the clinical course of depression: the 5 R’s
Phases of treatment
Treatment options
Adherence

Background
Two major issues to discuss
Chronic and recurrent nature of depression in general, with the need to handle depression as a chronic disease
Importance of chronic sub-syndromal depression

Chronic Major Depression
Symptoms qualifying for major depression lasting longer than 2 yrs
Residual - episode of major depression with persistent residual symptoms
Residual recurrent - recurrent episodes of major depression that do not remit between episodes

Other Forms of Chronic Depression
Dysthymia - fewer symptoms than major depression, present longer than 2 years
Double depression - episode of acute major depression superimposed on dysthymia

Course of Major Depression
10-year prospective study of episodes of major depression -
18% recovered from the episode and remained well throughout the period
7% remained ill throughout
28% had recurrence within 1 year
62% recurrence within 5 years
75% recurrence within 10 years

Impact of Depression
Very significant long-term impairment
Medical Outcomes Study - general, physical, and social health functioning worse in depression than in most other chronic general medical conditions
Lots of somatized physical symptoms
Use of health services very high
Economic cost estimated in 1990 at $43.1 billion per year

Impairment from Chronic Depression
Chronic forms of depression especially disabling
20% with chronic depression unemployed, 31% employed in jobs significantly below their education and training level
High level of psychiatric comorbidity
Lifetime diagnoses in dysthymia patients: 68% develop major depression, 26% panic disorder, 68% anxiety disorder, 24% substance abuse

The “Five R’s”
Response - significant reduction of symptoms below threshold for major depression
Remission - a reduction of symptoms to the point of “wellness”
Recovery - sustained remission
Relapse - exacerbation of symptoms after a response or remission but before recovery
Recurrence - a new episode after recovery

Two Additional “R’s”
Refractory - lack of response to multiple interventions of ordinarily adequate treatment
Residual - minor or sub-sydromal symptoms despite treatment

Phases of Treating an Episode
 of Depression
Acute phase - aims at maximum reduction of symptoms to achieve remission
Continuation phase - after remission of an acute episode - aims to prevent relapse of symptoms, move to recovery
Maintenance phase - after recovery in high risk patients - aims to prevent recurrence

Acute Phase of Treatment
Key issues include using sufficient dosages, monitoring the patient closely, changing to new medication if response inadequate
If a medication is going to be effective, should see reduction of symptoms within 4 - 6 weeks
Acute phase (achieving stable response, remission) usually takes 8 - 12 weeks

Continuation Phase
40 - 60% risk of relapse if medication is stopped in the first few months of treatment
Continued treatment reduces risk to 5 - 10%
Tricyclics and SSRI’s studied for continuation therapy; work equally well; side effect profile, compliance substantially better for SSRI’s

Guidelines for Continuation Therapy
Continuation therapy should be withdrawn only after patient is asymptomatic 16 - 20 weeks, including mild symptoms
Medication should be used at full acute phase dosage level
Medication should be withdrawn slowly
Monitor patient closely
Educate patient and family to recognize early signs of recurrence

Maintenance Phase
Goal - prevent new episodes in high risk patients
Generally use the same dose of the same drug that the patient responded to in acute phase
Consider and discuss risk factors early in the course so that maintenance can be planned then instead of right before the patient expects to discontinue the medication

Risk Factors for Recurrence
The more episodes, the more likely a recurrence
People with 3 prior episodes have 3 year recurrence risk of 85% without maintenance
Family history of bipolar or recurrent major depression
First episode at age less than 21 or greater than 60

More Risk Factors for Recurrence
Severe prior episode
Prior episode difficult to treat
Closely spaced prior episodes
Incomplete recovery between episodes
Patients with double depression
Patients with multiple comorbid conditions

Length of Maintenance Therapy
Should last at least 4 - 5 years, perhaps lifelong; not much data to help with decisions on length
Across first 3 - 5 years of maintenance treatment - risk of failure of medication about 10% per year; risk of recurrence off medication 30 - 50% in first 6 months after discontinuation

Discontinuation
If decision is made to discontinue -
Slow taper of medication probably better (1 - 2 months?)
Educate patient and family about early signs of recurrence
May consider counseling to help with transition

Counseling in Maintenance
Psychotherapy important in maintenance phase - deal with marital, family, social problems, history of abuse, or ongoing domestic violence
Supportive counseling by primary care physician also important component
Seek to develop physician - patient - family partnership
Office nurse, therapist, others can also be valuable partners in integrated approach

Patient Education in Maintenance
Educate patient & family about depression as a chronic disorder -
risk of recurrence,
need for ongoing treatment despite improvement,
treatment risks & benefits,
signs and symptoms of recurrence,
 stigma issues

Dysthymia
Chronic (at least two years) symptoms of depressed mood most of the time; only two other depression symptoms required
Much higher risk of developing major depression - 90% lifetime prevalence
Onset tends to be early in life
Adverse life events, abuse issues very important

Diagnosis of Dysthymia
50% or less ever treated
Even more difficult to recognize than major depression
Patients generally present with other complaints
Chronic, non-acute nature of symptoms - patients may not even recognize the extent
Sleep disturbance might be a red flag
Check for subclinical hypothyroidism

Treatment of Dysthymia
Not much data available
Some suggestion that serotonergic antidepressants may be more effective
Some suggestion also that counseling may be more important in dysthymia than in major depressive episodes
May be slower to respond than major depression
Optimal duration of treatment unclear; probably should be taken indefinitely

Double Depression
Major depression episode on top of antecedent dysthymia
When major depressive episode portion resolves, patient usually returns to dysthymia rather than an asymptomatic state
More relapses/recurrences over the subsequent two years than in major depression alone

Summary of Main Points
Increasing evidence that major depression commonly follows a chronic course
Should be managed as a chronic disease
Phases of treatment - acute, continuation, maintenance
Dysthymia - also a big problem; major depressive episodes common and difficult
Monitor patients closely for recurrence
Many require long term maintenance