|
Contributed
by: Roger S. McIntyre,
MD, FRCP(C) After completion of this case, participants will be able to:
Patient Presentation You determined
today that the sertraline has effected a partial remission: Ms.
B. finds herself crying less frequently, her energy is slightly
improved and she is coping more effectively at work. However, she
continues to have negative thoughts, a poor appetite, and low energy,
and all phases of her sleep, particularly remaining asleep, are
disrupted. She is not suicidal. Questions
to Consider:
On further review,
Ms. B. denies panic attacks, phobias, obsessions or compulsions.
She denies any other major anxiety symptoms, and also denies any
past history of hypomania, mania or psychotic features, or abnormal
eating behaviours. She was briefly treated at age 18 with a tricyclic
medication for a situational depression, but took this medication
only for a short while, as she could not tolerate it. She spontaneously
tells you that she has not been misusing alcohol or illicit substances
as her father had several medical complications from misusing alcohol.
Other than her father's alcohol misuse, there are no other known
psychiatric disorders in the family. Questions to Consider:
You ask Ms.
B. to increase the dose of the sertraline to 150 mg daily. After
three weeks, she returns, having noted no change in the depressive
symptoms. She is reluctant to go higher with sertraline as she accidentally
took 200 mg two days ago and felt persistent nausea, but wants to
continue with this medication because she feels that she has partially
benefited from it. Questions to Consider:
After you review
the various strategies available, Ms. B. chooses to undertake a
trial of adjunctive lithium carbonate. You begin this medication
at 600 mg daily; after a week her plasma lithium level is 0.64 mmol/L.
She is tolerating the regimen well but has not yet noted any antidepressant
effect. Questions to Consider:
After two more
weeks of lithium augmentation, little has changed. Ms. B. continues
to experience depressive symptoms and is particularly distressed
because her supervisor has noticed her frequent careless errors
– a marked difference from her job performance before the onset
of this depressive episode. This is her longest-held job, and she
wants to advance within the company. Ms. B. asks you if you can
hasten the antidepressant response. Questions to Consider:
Once again,
you review the treatment options with Ms. B. She chooses to discontinue
sertraline and begin a trial of venlafaxine XR 75 mg daily, increasing
the dose to 150 mg daily. By the four-week mark, she has still not
noticed a significant symptomatic or functional change. After you
increase the dose to 225 mg daily, Ms. B. feels a significant improvement
in her mood, energy, and level of agitation. She is still bothered
by negative thoughts, disturbed sleep and loss of appetite; her
libido has decreased and she is now anorgasmic. Her blood pressure
is normal. Questions to Consider:
After a review
of available strategies, Ms. B. elects to try a combination of venlafaxine
XR 225 mg daily and bupropion SR 100 mg daily. She attains full
symptom remission and partial, but significant, improvement of her
sexual dysfunction. Questions to Consider:
Discussion: It is also essential
that the clinician select an antidepressant with the greatest therapeutic
potential – the best likelihood of achieving remission of symptoms,
improving functioning, and promoting a recovery. A reasonable trial
of an antidepressant should comprise four to six weeks of an adequate
dose, if the patient is adherent to the treatment. The dose may
be increased until either the patient responds or side effects preclude
further increases. To enhance compliance, the patient should be
educated about the expected adverse effects, the usual time course
of response, and implications for treatment. Patient expectations
about treatment should be directly addressed with factual information. While response
rates of 50-60% are common with antidepressants, remission rates
obtained with SSRIs are typically much lower – on the order
of 20-30%. Furthermore, even among adherent patients who achieve
remission and continue on adequate antidepressant doses for up to
two years, 10-25% may experience a recurrence. Therefore, augmentation
and combination strategies may be relevant for up to half of depressed
individuals. If there has been no response at all to the index antidepressant,
it may be more appropriate to switch medications than to pursue
augmentation strategies. Patients should be educated about wash-out
periods (typically five half-lives), discontinuation symptoms, potential
exacerbation of depressive symptoms, potential loss of a previously
established response, the inability to predict subsequent antidepressant
response, and the adverse event profiles of the new agent that is
to be introduced. Augmentation
refers to the addition of a compound whose primary indication is
not antidepressant, while combination denotes co-administration
of two or more primary antidepressants. Generally speaking, augmentation
is used to boost a partial remission; agents commonly used for augmentation
include lithium, T3, and buspirone. Frequently used combinations
include SSRI+TCA or SSRI or SNRI+bupropion. When augmenting or combining,
the clinician should pay careful attention to drug-drug interactions
mediated by the CYP450 system. Combinations containing MAOIs are
generally discouraged. The notion of
switching to a new antidepressant if no response is seen –
but using combination/augmentation strategies if a partial remission
is seen – has heuristic value, but has not been empirically
confirmed. It has been suggested that adjunctive cognitive therapy can reduce residual symptoms as well as the long-term risk of recurrences. After acute treatment has succeeded, the clinician will need to educate patients to distinguish between flurries of depressive symptoms and full-blown relapse or recurrence. Proceed to Section IV - "Clinical Cases - Case #3"
|
