By Neil Sandson, MD
[Spring 2006; Vol. 32, No. 3; Pg 6, 10]
Bipolar
disorder is one of the most challenging illnesses that psychiatrists encounter
in patients. Prior to
2000, only lithium, valproate, and chlorpromazine were
FDA approved for the treatment of bipolar disorder.
Since then, eight more agents (aripiprazole, carbamazepine, lamotrigine,
olanzapine, olanzpine/fluoxetine combination, quetiapine, risperidone, and
ziprasidone) were approved. While
there are patients who are responding better to pharmacotherapy than in the
past, our more expanded armamentarium makes adherence to evidence-based practice
more important than before,
to prevent us from straying into uncharted and potentially dangerous territory.
One
trend I have observed over 10 years, is a tendency for pharmacotherapy to be
guided by (seeming) avoidance of risk and a desire for “newer and better”
drugs rather than using a drug with superior efficacy.
This accounted for the popularity of gabapentin in the treatment of
bipolar patients. Unfortunately,
variations of this theme persist.
One example is the underuse of lithium, despite research showing that it
has the best outcome in the treatment of all phases of bipolar illness, not to
mention an unmatched antisuicidal effect in bipolar patients.
Another example is the use of drugs like oxcarbazepine and topiramate as
first and second-line drugs in bipolar pharmacotherapy.
There is no evidence to support this practice, and yet these agents are
used far more frequently than either their demonstrated efficacy or their
ancillary benefits (avoidance of bone marrow suppression and drug interactions
with oxcarbamazepine and weight loss with topiramate) would justify.
This is not to suggest that these agents can never be used for a bipolar
patient. Rather, they
should be used with a reluctance that reflects their highly conjectural status
as helpful drugs.
Another
difficult issue in the treatment of bipolar disorder is the problem of bipolar
depression and the appropriate role of antidepressant medications in the
depressed and maintenance phases of the illness.
There are many, like myself, who are particularly averse to using
antidepressants as a standard intervention.
Of concern is the propensity of these drugs to produce switches into the
manic phase, which is disruptive to patients’ lives and may lead to further
deterioration in the course of their illness.
It is also true that bipolar
depression is responsible for more morbidity and mortality.
Thus, many reasonable clinicians maintain that effective treatment and
prevention of bipolar depression is a higher clinical priority than the
prevention of manic episodes.
My perspective on this issue is that combination “mood stabilizer”
therapy (liberally including lithium, various anticonvulsants, and antipsychotic
agents) addresses both clinical concerns.
No study has definitively demonstrated that antidepressants are superior
in treating bipolar
depression than combination mood stabilizer therapies, and some studies suggest
that they are comparable in efficacy.
Given that both approaches seem equally effective for bipolar depression,
I have pursued combination mood stabilizer therapies as my first treatment
option for bipolar depression; this avoids the risk of using an antidepressant
that may cause a switch to mania.
Some
point out that the newer antidepressants, such as SSRIs and bupropion, have
manic switch rates comparable to placebo in double-blind, placebo-controlled
studies. However, I
have observed that switch rates seem higher in clinical populations as compared
to patients able to meet the stringent exclusion criteria characteristic in
rigorous studies. Thus,
the dangers posed by antidepressants may well be greater than more reliable
studies would suggest.
A
caveat to the above is to respect prior treatment responses for specific
patients. Altshuler
et al. recently published a study that suggests that if a patient maintained
good stability for at least two months while on an antidepressant, then removing
that antidepressant is more likely to produce de-compensation.
In view of this finding, and the broader philosophical principle of
“never change a winning game, always change a losing game”, I don’t remove
the antidepressants from stable patients’ regimens in a dogmatic or cavalier
manner. I’ve even
been known to voluntarily prescribe them for bipolar depression from time to
time.
One
final issue with regard to evidence-based treatment of bipolar disorder is the
neglect of non-pharmacologic interventions.
Over the past five years, research has proven that cognitive-behavioral
therapy and individual and family psycho-education are efficacious in preventing
relapse across populations. While
most clinicians are generally aware that combined approaches are “better”
than either medication management or psychotherapies alone, there is also a
pervasive sense that medication management by itself is “good enough” for
many or even most bipolar patients, and that only our most treatment resistant,
disruptive, and/or noncompliant patients really require both forms of treatment.
Regrettably, this devaluing of psychotherapy is a generalized phenomenon that is
not restricted to the treatment of bipolar disorder.
It has its roots in the economic and philosophical changes that have
altered our professional mode of practice over the last 15+ years, and systemic
problems continue to hinder even the most well-intentioned clinicians from
implementing psychotherapy. However,
help may be on the way.
The
STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) study is
a large, multicenter, NIMH study designed to evaluate the efficacy of various
medications and
psychotherapeutic/psychosocial interventions in the treatment of bipolar
disorder. While the
publication of the phase one results of the CATIE (Clinical Antipsychotic Trials
in Intervention Effectiveness) study has not instantly transformed the treatment
of schizophrenia, it has represented a decisive step toward evidence-based
practice. In
the February 2006 issue of the American Journal of Psychiatry, some initial
analyses from the STEP-BD study were published.
These dealt mainly with specific factors that were associated with
illness recurrences, but in the near-future, more specific comparisons of
therapeutic interventions will be published.
These results will hopefully exert a significant influence on current
practice.