Mood Stabilizers and Mood Swings: In Search of a Definition
LyndaNP
From:
http://www.mhsource.com/pt/p991036.html
Mood Stabilizers and Mood Swings: In Search of a Definition
by Simon Sobo, M.D.
Psychiatric Times October 1999 Vol. XVI Issue 10
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Mood-stabilizing drugs slipped into the vocabulary of psychiatrists
during the last 15 years without a proper discussion of their
definition. Consequently, these medications have been used in ways that
have no empirical justification. The original idea behind the term mood
stabilizer was the apparent ability of lithium to offer antimanic
qualities as well as some measure of antidepressant action. The American
Psychiatric Association's Practice Guideline for Treatment of Patients
With Bipolar Disorder (1994) defines mood stabilizers as "medications
with both antimanic and antidepressive actions." From time to time,
research has been contradictory about the efficacy of lithium as an
antidepressant (Keck and McElroy, 1996). However, the concept was clear.
This is not the case with the various anticonvulsant medications that
have been labeled mood stabilizers. Despite widespread use, it is not
obvious what is meant by a mood stabilizer and how anticonvulsants fit
that description.
There is little if any clear-cut evidence that valproate (Depakote,
Depakene), carbamazepine (Tegretol) (Kalin, 1996-1997) or gabapentin
(Neurontin) are effective antidepressant agents. Yet as soon as they
were shown to have efficacy in acute mania, they were quickly labeled
mood stabilizers rather than antimanic agents.
This is not a matter of small significance, since it is not unusual for
bipolar patients with a predominantly depressive history to be
exclusively put on mood stabilizers with the expectation that the
depression will be treated, and that rapid cycling due to the use of
traditional antidepressants will be avoided. I'm not referring to the
prophylactic use of mood-stabilizing agents when it is expected that
antidepressants will later be necessary so that protection against a
potential manic episode seems judicious. Frequently, mood stabilizers
are used as the sole antidepressant. Indeed, an expert consensus
treatment protocol recommends mood stabilizers alone as a first-line
approach in treating milder major depressive episodes in bipolar I
disorder and as a second-line approach in bipolar II disorder (Frances
et al., 1996).
Some experts such as Bowden (1996) and Keck and McElroy (1996) are so
concerned about the possibility of rapid cycling that they go still
further, considering the use of antidepressants as a last resort in
treating bipolar depression only after multiple mood stabilizers have
been tried first. While the concern about antidepressants causing rapid
cycling is based on an indisputable clinical possibility, these experts
have no illusions about the effectiveness (or indisputable evidence for
the effectiveness) of anticonvulsant medications as treatment for acute
bipolar depression. Both valproate and carbamazepine did little better
than placebo in the studies they cited, but if I understand them
correctly, they considered bringing relief from the torment of
depression as quickly as possible a less important priority than not
iatrogenically causing mood instability.
According to Gary S. Sachs, M.D., the definition of the term mood
stabilizerdoes not require antidepressant or antimanic efficacy, per se,
merely that the medication "decrease vulnerability to subsequent
episodes of mania or depression" and not exacerbate the current episode
or maintenance phase of treatment (1996). The use of anticonvulsant
medicines as mood stabilizers has become even more relevant since the
expansion of the bipolar disorder (BD) diagnosis to include bipolar II
patients (American Psychiatric Association, 1994). Bipolar II is a
reasonable addition to the nosology of mood disorders, sometimes
allowing earlier recognition and an appropriate alertness to the softer
signs of the illness. However, it also has contributed to an excessive
looseness in diagnosing BD. On more than one occasion, I have had
patients hospitalized for severe depression and, after a three- or
four-day stay, they have returned on a mood-stabilizing agent and
nothing else. They have been told that they have bipolar disorder and
that their anticonvulsant medication treats the basic problem.
Here is an example. Ariel, a 16-year-old girl, had a history of repeated
severe suicidal depressions punctuated by periods of a few hours,
sometimes a day or two (definitely not four days as specified in the
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
for hypomania), in which she felt a bit giddy as well as more social,
energetic and creative. There was no family history of manic-depressive
illness. She did not feel that her "up" times were a problem. Indeed,
she was able to perform at a high level academically and felt more
connected to her friends and parents. There was no pressured speech,
flight of ideas or a sense that her mind was racing. There was no
distractibility; impulsivity; irresponsible spending, driving or sexual
behavior; or loss of judgment. Insomnia was not present, and there was
no history of a decreased need for sleep. Although there was an
improvement in self-esteem, it was not inflated or grandiose. Ariel's
parents and friends, as well as Ariel herself, considered her good moods
entirely normal and delighted in them.
The arguments for and against using a loose definition of BD hinge on
the risk/benefit ratio of active treatment. On the benefit side, at
least theoretically, is the kindling model for bipolar disorder. It is
hoped that the prevention of frequent manic episodes may prevent rapid
cycling that often develops later in the illness. But this is theory,
not fact. Even when the diagnosis is clearly bipolar, there's no
empirical documentation and no longitudinal studies that demonstrate
long-term administration of medications will prevent rapid cycling later
in the illness. Despite this lack of proof, when a bipolar diagnosis is
unequivocal, treatment is a no-brainer. We treat vigorously with the
hope there will be this eventual benefit because good acute control is
desirable anyway.
When the diagnosis is based on looser criteria, it is a more complicated
issue. There are at least two prospective studies demonstrating that
patients with major depressive disorder and a definite family history of
BD have a very high risk for transformation to bipolar I disorder
(Akiskal et al., 1983; Strober and Carlson, 1982). Clearly in this
situation, it is advisable to monitor patients with serious depression
closely for early signs, even more so when there are soft signs of
hypomania. But if there is no family history, a case can be made to hold
back on treating the patient's not diagnostically definable highs.
From this vantage point, if a patient such as Ariel does not have
symptoms that she, her family and friends, or any layperson, would
consider symptoms, what are we treating? If we believe that we are
somehow correcting a fundamental chemical imbalance, there would be a
rationale. But we don't know what the chemical imbalance(s) is (are) in
bipolar disorder. We don't really know what mood stabilizers do for the
illness. Even our guesses hint at diverse possibilities. Thus, valproate
seems to have an effect on ?-aminobutyric acid (GABA) receptors, and
gabapentin may increase brain levels of GABA. In contrast, the proposed
mechanism of action for carbamazepine and lamotrigine (Lamictal) is
voltage-dependent inhibition of sodium currents. The latest speculations
about lithium are that it is affecting G-proteins, that it exerts a
push/pull effect on the neurotransmitter glutamate (Dixon and Hokin,
1998; Lenox et al., 1998), or that it alters sodium transport in nerve
and muscle cells and effects a shift toward intraneuronal metabolism of
catecholamines (Physicians' Desk Reference, 1999).
Diverse research hypotheses are a good thing, but they are not the same
as hard knowledge. How can we argue that we are treating at a
fundamental, etiological level of the illness when we don't know what
the chemical problem is, when our best guesses about how various mood
stabilizers work are that they work differently from each other, and
when we don't know how these proposed mechanisms might or might not be
related? Moreover, we don't have clear proof that we will prevent the
eventual development of the DSM-IV illness; even in the treatment of the
DSM-IV illness, we don't yet know if we are altering its long-term
course. All we do know is that we have good-not great-medications that
help control symptoms.
Hagop S. Akiskal, M.D., makes the strongest argument for a liberal view
of a very broad bipolar spectrum of abnormalities. He believes DSM-IV is
far too limiting and would include a bipolar III and a variety of
conditions under the bipolar umbrella (Akiskal, 1996; Akiskal and
Mallya, 1987). This position is not absurd in the sense that when we
eventually understand the genetics and biology of manic-depressive
illness, we may discover fundamental relationships. However, DSM-IV is
not a true collection of illnesses defined by etiologies. It is a
collection of disorders about which committees decide certain symptoms
should be clustered with the hope that someday, true etiological
understanding will correlate with these clusters or future clusters as
the evidence indicates. The issue here is using medications that may
only be working on symptoms (and possibly or probably not etiology or
pathogenesis) in patients who do not have symptoms as defined by
themselves or reasonable laypeople. In Ariel's case, she was suffering
from depression and was given a treatment that has not been shown to be
effective for depression.
On the risk side of the equation, the danger of unnecessary medication
is obvious with carbamazepine because of the possibility of aplastic
anemia and agranulocytosis. While this is rare (six patients per 1
million population per year for agranulocytosis and two patients per 1
million population per year for aplastic anemia), if carbamazepine is
used by enough psychiatrists over enough years for unjustifiable
purposes, there will be deaths that might not have occurred. In the case
of valproate, hair loss, weight gain, fatigue and, most recently, the
threat of polycystic ovaries, favors caution in a patient such as Ariel.
Tiredness and, sometimes, hypersomnia are not uncommon even at
therapeutic levels and contribute to treatment noncompliance. A huge
number of patients whom I have followed after inpatient stays with an
equivocal diagnosis are sleeping 14 hours a day. Of course, it does not
help that locally the standard regimen resulting from these
hospitalizations seems to also include Zyprexa (olanzapine).
Ariel did have "mood swings." She would be in a perfectly good mood and
then suddenly, with relatively minor provocation, switch to sadness,
irritability or an outburst of anger. This was the other major
justification for placement on a "mood stabilizer." There's only one
problem with this. The use of the term mood swingsin bipolar disorder
has usually referred not to labile affect, but to relatively long
stretches of depression or mania lasting weeks or months-although
occasionally days-which would then swing to the opposite.
While it is true that mixed episodes are not rare and may be
characterized by very rapid shifts in mood over the course of a day,
mixed episodes may also consist of a vague blending of both euphoric and
dysphoric themes. In any case, until recently, the term, mood swings,
did not refer to volatile moods.
Apparently, however, without a discussion in the literature of this
changed definition, mood swings have come to mean labile affect.
Similarly, rapid cycling-defined in the DSM-IV as four or more switches
in a year-not infrequently appears in clinical summaries when what is
being described are labile moods.
At first, I thought the problem was our local inpatient unit and a
mistaken reading of DSM-IV by one doctor in particular. If that were the
case, there would be no reason for this article. It soon became apparent
that similar diagnoses were being made at three other inpatient units
that I have contact with, including two prominent academic centers. I
have questioned several nurses on these wards and learned that most
misbehaving, impulsive teen-agers (once characterized as rebellious) are
now being diagnosed as bipolar. At an outpatient alcohol rehabilitation
center, a counselor told me the same thing was happening there. Erratic
moods and behavior were being called mood swings, and thus had become
bipolar symptoms. Moreover, the new use of the term mood swings had been
embraced by the other psychiatrists in town who were doing strictly
outpatient work. Social workers and psychologists were asking, as never
before, for medication evaluations for bipolar disorder on the basis of
mood swings, and many patients were self-referring themselves for mood
swings, having read about them on the Internet.
The typical story I heard when I questioned a patient with mood swings
was something like the following: "I'd be in a perfectly good mood at a
party but then would feel like going home. When my boyfriend gave me a
hard time, I'd let him have it." Or, "I would be doing fine shopping at
the supermarket. Suddenly, someone would cut in front of me in line, and
I'd go ballistic." Or, "I'd be getting along with my parents at home.
Then my father would say something, and I'd go stomping off to my room."
Sometimes, there would be no external event at all, but the patient
would notice a dramatic shift in mood from when they woke up feeling
fine to later in the day when they were feeling down.
Generally, in all of these cases the patients had almost no
introspective capacity. They had never attempted on their own, or been
encouraged by their psychiatrist, to make sense of the personal meaning
of their father's comment, or why their boyfriend made them so angry by
refusing to come home from the party and so forth. As far as they were
concerned, their behavior was totally incomprehensible and beyond their
control. They were relieved to hear that the explanation for their
difficulty was a chemical imbalance because, not only would it no longer
be their fault, but just as importantly, it could now be fixed.
Undoubtedly, over time, some of the impulsive and/or moody adolescents
now being diagnosed bipolar II on the basis of their mood swings will
later prove to be suffering from manic-depressive illness. This may turn
out to be true of Ariel.
Kramlinger and Post (1996) described clear-cut bipolar patients who were
followed on a ward and rated for mood every two hours during the course
of a day. They found a group of five patients who went up and down
throughout the day and wondered whether these represented "ultra-ultra
rapid cycles or ultradian cycling." However, this interesting
observation is a far cry from the routine labeling of volatile patients
as bipolar.
There is another contributing issue to what I believe is the
overdiagnosis of BD. In addition to "mood swings" being used as the
basis for diagnosis, irritability has gained new status. It has always
been appreciated that irritability, rather than euphoria, can be part of
a manic episode. But one would assume that irritability by itself would
not be the basis for diagnosing bipolar disorder in an unhappy teen-ager
or depressed individual, especially since irritability is found much
more commonly in depression than in mania. However, I am discovering
that many psychiatrists are using this criterion quite freely,
especially with patients who have labile affect, and are basically
making the diagnosis on a hunch.
Although the considerations above regarding risk/benefit ratio still
apply, ordinarily I would have no difficulty with a clinician following
a clinical intuition and diagnosing atypical BD now and again when full
criteria were not met. The problem is, if my observation of local
practice patterns hold elsewhere, such hunches have become routine,
especially in the rapid-turnover inpatient wards that now characterize
our mental health system. It has become the diagnosis du jour. Observing
practice patterns in Penn Valley, Pa., psychiatrist David Behar, M.D.,
in a letter to Clinical Psychiatric News (1998) described bipolar
disorder as being absurdly overdiagnosed. "Any overreacting patient now
gets the label and a mood stabilizer," he said.
If this is the case nationally and not just in the Northeast, it is
reasonable to look for an explanation. We also must include the pressure
on outpatient psychiatrists from referring therapists who themselves are
under pressure from health maintenance organizations and mass media
articles that foster patient expectations of rapid results. The
psychiatrist is placed in a situation not dissimilar to some family
doctors who would prescribe antibiotics for the common cold so the
patient would feel the doctor "did something." Pressure also comes from
the occasional therapist who doesn't like their diagnostic acumen
questioned and will refer elsewhere if the patient doesn't receive
medication for mood swings. This can be likened to schoolteachers who
want their unruly students labeled as having
attention-deficit/hyperactivity disorder and Ritalin (methylphenidate)
prescribed.
Ultimately, the problem may be language itself. Even when a bipolar
diagnosis, per se, is not considered, having a category of drugs called
mood stabilizers lends itself quite well to a belief that it is a valid
approach to moodiness. In this case, the issue is not whether
anticonvulsant, antimanic medications deserve to be called mood
stabilizers in bipolar disorder, but rather that the termmood
stabilizers conveys the impression that they are a perfect fit for
volatile, overemotional patients.
As noted, alcohol and drug abusers are now very often being diagnosed
with bipolar disorder, once again because labile affect, a common
finding in alcohol and drug abusers, is being called mood swings. One
factor contributing to this is our better appreciation of how many
bipolar patients abuse alcohol and drugs. However, in the absence of a
clear-cut history, I don't know how a bipolar diagnosis can be made
until the patient has been off intoxicants for a reasonable period of
time. Rapid shifts in mood have always characterized the behavior of
alcohol- and drug-abusing patients as well as those recovering from
addiction. What is gained by the bipolar label? Some alcoholic patients
like it because it "explains" their lack of control. Like genetic
theories of alcoholism, it shifts blame and gives an external enemy to
fight against. However, these should not be the reasons for us to make
the diagnosis.
Mood lability is also an important component of borderline personality
disorder (BPD) and here, too, an unusual number of patients are being
diagnosed bipolar on the basis of their mood swings. Granted one can
legitimately make a case, as Akiskal does, that borderline personality
disorder is fundamentally an affective disorder and possibly a variant
of bipolar disorder (1996). In the case of BPD, the ravages of this
diagnosis are so extreme, and so many of our treatments are ineffective,
that I see nothing wrong with trying one of the anticonvulsant
medications on an empirical basis. However, in my experience, high doses
of selective serotonin reuptake inhibitors seem to work far better for
labile affect, probably because of their ability to alleviate
frustration and dull passions rather than from an antidepressant action,
per se.
To summarize, there are three important questions:
1) Are rapidly shifting moods (now mislabeled as mood swings)
particularly diagnostic of bipolar disorder?
2) Are mood-stabilizing medications useful in patients with rapidly
shifting moods whether or not they are truly bipolar?
3) What is the mechanism of action of the anticonvulsant medications
that make them useful in psychiatric conditions?
Question 1: I do not know if rapidly shifting moods are a typical
feature of manic-depressive illness. My clinical impression, after close
to 30 years of practice, is that they are not uncommon, both before
other symptoms have become manifest and afterward. But rapidly shifting
moods are far more common in the instances already discussed: unhappy or
rebellious adolescents, alcoholics and drug abusers, and those with
borderline personality disorder. Whether the mood changes during the
course of a day seen in mixed episodes of bipolar patients constitute
ultradian cycling or are simply what typically constitutes mixed
episodes has to be settled (Kramlinger and Post, 1996).
Regardless of the outcome of that issue, I think we have to address the
separate issue of whether the presence of mood lability should raise our
index of suspicion for manic-depressive illness in moody adolescents,
borderlines, alcoholics and others with short fuses. (It should be
emphasized that Kramlinger and Post's ultradian cycling referred to
ratings of mood systematically made every two hours and not sudden mood
shifts.)
Questions 2 and 3: Ironically, despite the unfocused use of the term
mood stabilizer described earlier in this article, I think clinicians
may have found a legitimate use for anticonvulsant medications in
psychiatric practice. The literature includes theories that GABAergic
mechanisms may play a role in depression (Petty, 1995; Petty et al.,
1996). From time to time, various benzodiazepines have been claimed to
have antidepressant efficacy. This might be due to the hypothesized
fundamental chemical relationship between GABA and mood. Or, it might be
an indirect result of their tranquilizing function. After all, patients
with panic disorder often develop depression secondary to their lost
sense of control and have an improvement in mood once benzodiazepines
have put out the fires. Similarly, some patients with agitated
depressions experience anxiety as the most distressing part of their
syndrome and find their mood improves, even before antidepressants kick
in, when benzodiazepines have provided relief from their anxiety.
If there is a fundamental relationship between GABAergic mechanisms and
mood, then the use of valproate and gabapentin might eventually be
empirically shown to have antidepressant action, and my earlier
denigration of the term mood stabilizers would be misplaced. The term
would legitimately apply to these anticonvulsant medications in its
traditional sense. However, since carbamazepine and lamotrigine are not
believed to work through GABAergic mechanisms, and they are mentioned in
the same breath with the other mood stabilizers, my best guess is that
the quality that anticonvulsant medications have in common is that they
are calming agents or tranquilizers. They may represent the long-sought
effective, nonaddicting tranquilizers. (There is some support for
valproate's anxiolytic-like function in animal research [Dalvi and
Rodgers, 1996; de Angelis, 1995].)
On an intuitive level, it makes sense that anticonvulsant medicines,
whatever their mechanism of action, are calming. Indeed, if we picture
seizures as "a massive discharge of neurons," it is not much of a
stretch to think of the various psychiatric conditions where
anticonvulsant mechanisms are finding particular usefulness-explosive
disorder, mania, panic disorder, borderline personality disorder-as
conditions that may possibly have analogous massive discharges of nerve
impulses. And one step down from that, one could imagine that mood
swings, as the term is being used today for those with fiery
temperaments, or those caught in the storms of adolescent turmoil, might
be attenuated by calming agents, with or without a bipolar diagnosis. In
other words, mood stabilizers help mood swings, as the terms are being
misused today. Eliminate calling the patients bipolar and not that much
harm is done. Valproate may deserve its widespread usage.
We are still left with the question of whether anticonvulsant
medications' calming action is necessarily working directly on mood.
This question is of some relevance because of the kind of backward
reasoning that seems to accompany the effective use of anticonvulsant
medications. For example, Stephen J. Donovan, M.D., has proposed that a
new diagnosis-explosive mood disorder (EMD)-be created and replace the
diagnoses of conduct disorder or oppositional defiant disorder in one
subset of patients-children with irritable mood swings-"because these
are sociological not psychological constructs. They do not identify what
is 'disordered,' suggest etiology or guide treatment" (Sherman, 1998).
And what was Donovan's basis for suggesting that the primary difficulty
is mood? Adolescents meeting the EMD criteria improved on the mood
stabilizer divalproex.
Similarly, because such agents as valproate and carbamazepine have been
found useful in recovering alcoholics does not necessarily support a
view that these patients are probably bipolar. Rather, the patients'
improvement might be the result of these agents' tranquilizing function.
This kind of thinking is entirely separate from whether or not
anticonvulsant medications have an antidepressant action.
Going out on a limb, I would argue that even in bipolar disorder, the
various anticonvulsant medications being used to control mania may not
be directly treating the elevated mood, per se, but rather treating the
intensity of mania, the exuberance of energy, racing thoughts and the
like. Just as patients with panic disorder often feel less dysphoric
when they regain control through the use of benzodiazepines, it is
possible that mood stabilizers could, with chronic administration, be
demonstrated to have an indirect antidepressant action by returning a
measure of self-control, rather than through a direct antidepressant
action. Certainly, many patients with BD rue the foolishness of their
mania, not to mention the broken marriages, lost friendships and jobs,
depleted bank accounts, and sheer havoc left in the wake of their
exuberance. Over a period of time, less havoc would serve as one less
stressor to precipitate dysphoria and depressive episodes.
Also, I have treated several bipolar I (mixed) patients who resembled
agitated depressives in their level of anxiety. Although admittedly a
small anecdotal sample, my personal impression is that these are the
only patients who have shown an antidepressant effect from divalproex.
My guess would be that it is the calming effect of the divalproex that
was helpful here rather than the antidepressant effect. Otherwise, from
pure chance, I would have seen more cases in which the divalproex worked
as an antidepressant. Moreover, considering the amount of research done,
one would expect by now to see good double-blind evidence of divalproex
antidepressant action (rather than the usual "soon to be published"
impression) if the effect were a robust one. I am also curious if,
within the studies showing that anticonvulsants have an acute
antidepressant action (in the range of 30% to 40%), there are data that
could be teased out regarding agitation. Did the responding patients
have greater amounts of agitation than other depressed patients?
Finally, before we get too excited about "better living through
chemistry," a word about mood swings of the adolescent variety. Classic
psychoanalytic concepts are more relevant than ever. The vicissitudes of
self-esteem regulation in many adolescents are closely linked to the
loss of an idealized authority figure (and accompanying culture) from
whom they can feel protection and confirmation. As they leave the cocoon
of their own family's world and values, they must replace it with a
stark and uncertain court governed by peer approval. It is a faddish,
unforgiving universe of shifting gurus and uncertain alliances that
plays havoc with mood until, with maturity, a more stable identity can
be established. This is not to mention the effect of changing hormones,
astonishing physical growth and emergence of sexual passion. Medication
may have a role to play during this transitional period. But I would
hope that psychiatrists have the wisdom to guide parents and children
appropriately through this difficult time, and not confuse matters with
scary diagnoses such as bipolar disorder and the use of chemicals that
work in ways that are poorly understood.
Dr. Sobo is in private practice in northwest Connecticut. His book, The
Fear of Death, will be published this fall.
References
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Akiskal HS, Walker P, Puzantian VR et al. (1983), Bipolar outcome in the
course of depressive illness: phenomenological, familial and
pharmacological predictors. J Affect Disord 5(2):115-128.
American Psychiatric Association (1994), Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, D.C.:
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Behar D (1998), Bipolar overdiagnosis. Clinical Psychiatry News
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Dalvi A, Rodgers RJ (1996), GABAergic influences on plus-maze behaviour
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Dixon JF, Hokin LE (1998), Lithium acutely inhibits and chronically
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Frances A, Docherty JP, Kahn DA (1996), The Expert Consensus Guideline
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LyndaNP
Reality isn't the way you wish things to be, nor the way
they appear to be, but the way they actually are.
- Robert J. Ringer
Chris Malcolm
>From:
>http://www.mhsource.com/pt/p991036.html
>Mood Stabilizers and Mood Swings: In Search of a Definition
>by Simon Sobo, M.D.
>Psychiatric Times October 1999 Vol. XVI Issue 10
This is a most interesting article, interesting in its description of
the rather vague hunches and loose definitions of terms that have
crept into psychiatric diagnoses of manic depression, interesting in
its good and praiseworthy attempt to restore some principled clarity
to the terminology of diagnostic criteria in this area, and also
interesting in its lack of any principled model on which to base such
a clarification.
There is in fact a very simple well known model which can provide some
useful insights into the diganostic criteria and classification of
medications for manic depression. The problem is that it is very well
known to physiscists, mathematicians, electronic engineers, and
cyberneticians, but unfamiliar to psychiatrists.
The key is contained in that well known phrase "mood swing", which
suggests something which swings like a pendulum. The interesting thing
which Galileo discovered about pendulums was that they had a tendency
to swing with the same period, regardless of how large or small was
the swing. That was what made them useful in clocks. This is in fact a
general property of a special kind of system which has some kind of
mechanism for moving back towards a central stable point from which it
has been displaced. If the restoring force is proportional to the
amount of displacement, then the system will swing back and forth with
a constant cycle period regardless of the size of the swing.
This happens in some mechanical oscillations, such as pendulums or
bouncing springs. It happens in some electrical oscillations, such as
the resonant tuned circuits of capacitor and inductor which we often
employ in radio receivers to tune in particular radio stations. It
happens in some chemical oscillations, such as the famous
Belousov-Zhabotinski reaction.
In some cases we want the swinging to go on for ever, such as in a
clock. In that case we try to make a mechanism with as little
frictional and other losses as possible, and add a little impetus to
it to make up the residual losses we couldn't remove (because
perpetual motion is impossible). That's how clocks work.
In some cases the natural oscillations of the system are very
annoying, and we want it just to move quickly to its stable central
point and stop there. That's the problem with using a magnet on a pin
as a compass to find North: it keeps wobbling back and forth. So
better compasses add viscous friction (which increases with speed)
which damps the oscillations so that the compass moves smoothly to
North and stays pointing there.
That's what we want our moods to do. They get disturbed by things
which depress us, such as loss, and which excite us, such as good
fortune, and we want them to recover back to normal in an appropriate
timescale without overshooting into the opposite mood. In other words
we want them to behave like a good fluid filled compass, and not like
the see-sawing back and forth of the air compass. We also want them to
do something more. We want them to adapt to changed circumstances. If
you were to be wrongfully imprisoned for a murder you didn't commit,
you might understandably be very depressed. For a while. But after
some time you would want to get over it and start planning how to get
out. In other words, given a depressing circumstance, you would think
it appropriate to be depressed for a while, but then to recover your
normal capable mood despite the continued existence of the depressing
circumstance. This is like asking a spring which has a heavy weight
placed on it to sink down for a while, and then to recover back to its
unweighted state.
A spring on its own can't do this, but control systems with external
sources of power can be devised which can, are very useful, and occur
in all sorts of biological systems. In the last century they have been
used in a variety of control systems engineered by us, such as
aeroplane autopilot systems. The theory of such systems is known as
control theory. Control theory shows us how to make control systems
which behave in the optimum fashion, and it shows us how broken
control systems behave, and how to fix them. The important concepts
are:
1. the goal state, which is where the system wants to be.
2. the displacement, which is how far it is from the goal state.
3. the displacement-proportional returning force, which
provides return in a constant time. This is known as the proportional
factor.
4. the gain, or amplification, which when less than one means
the system will eventually stop swinging, and if more than one, means
the system will swing more and more wildly until it hits some kind of
limit.
5. the damping, which has to be viscous or speed-proportional
damping if the constant time for returning to the goal state
regardless of displacement is to be preserved. This is known as the
differential factor because speed is derived from the difference
between two successive displacements.
6. Load droop, which causes a system to stop short short of its
goal because of some continuing external perturbation.
7. The integral factor, which fixes load droop by adding in
a decaying displacement summation factor.
The best behaved control systems have these three factors, the
proportional, the differential, and the integral, in the right
proportions. If the integral is inadequate we get load droop. If the
differential is missing we get oscillating swings back and
forth. Derived from these three is the system gain. In the optimum
control system, which returns as quickly as possible without
overshoot, if the damping provided by the differential is removed,
then the system gain becomes more than one, and not only does the
system oscillate if distruebed, but the oscillations get wilder and
wilder until something breaks or it hits a limit.
As should by now be obvious I'm suggesting that the mood swings
characteristic of manic depressive disorder, coupled with what we
expect a well behaved mood control system to do, suggest a mood
control system with too little or no damping. In fact, there are good
reasons for suggesting that mood control should be managed by a
variety of control systems of differing periods, such as daily,
monthly, and yearly. If so, then we would expect there to be a variety
of types of manic depressive disorder characterised by different
frequencies of mood swings, which would be affected by some
medications in different ways. Which, as it happens, is what we do
find.
>Mood-stabilizing drugs slipped into the vocabulary of psychiatrists
>during the last 15 years without a proper discussion of their
>definition. Consequently, these medications have been used in ways that
>have no empirical justification. The original idea behind the term mood
>stabilizer was the apparent ability of lithium to offer antimanic
>qualities as well as some measure of antidepressant action.
An antidepressant is something you take when depressed which stops you
being depressed. An antimanic is something you take when manic which
stops you being manic.
Unfortunately antidepressants don't seem to work like state
changers. It's not like deciding the soup lacks salt, adding salt, and
immediately it is salty enough. We are interfering with an active
control system, and what happens depends on how the whole control
system behaves. In particular, all control systems have
momentum. Adding an extra antidepressant push will have more effect
than just moving it out of depression, it will increase the speed with
which it moves through the goal point, and this extra momentum will
carry it on up the other side into mania. Adding extra forces at one
point in the swing is in effect turning up the system gain, increasing
the amount of push created by displacement. This will reduce the time
taken to get out of depression, but at the cost of increasing the
tendency toi swing up the other side into mania, and will also
increase the frequency of oscillation, i.e. decrease the period of the
mood swings.
As this model suggests they should, antidepressants are well known
(most of them) to shorten cycle periods, which suggests they do work
by increasing gain of a mood control system. This has an interesting
implication in their use as improvers of mood lability which I will
come to later.
There is another interesting effect of turning up the gain. In a
system with low damping which has critical gain, then turning up the
gain will turn what used to be a stable system into an oscillating
system. That's what antidepressants do too. It is called
"antidepressant-triggered mania". It only occurs in BPs, i.e., the
kind of people I suggest have low or absent mood control damping. This
too suggests that antidepressants work by increasing the gain.
Now let's consider mood stabilisers. The original definition was that
they were drugs which had both an antidepressant and an antimanic
capability.
>The American
>Psychiatric Association's Practice Guideline for Treatment of Patients
>With Bipolar Disorder (1994) defines mood stabilizers as "medications
>with both antimanic and antidepressive actions."
But something wasn't quite right about that idea.
>From time to time
>research has been contradictory about the efficacy of lithium as an
>antidepressant (Keck and McElroy, 1996). However, the concept was clear.
>This is not the case with the various anticonvulsant medications that
>have been labeled mood stabilizers. Despite widespread use, it is not
>obvious what is meant by a mood stabilizer and how anticonvulsants fit
>that description.
>There is little if any clear-cut evidence that valproate (Depakote,
>Depakene), carbamazepine (Tegretol) (Kalin, 1996-1997) or gabapentin
>(Neurontin) are effective antidepressant agents. Yet as soon as they
>were shown to have efficacy in acute mania, they were quickly labeled
>mood stabilizers rather than antimanic agents.
Quite properly so, because some patients end up being stabilised just
by taking one of these stabilisers. But if some stabilisers aren't
antidepressant, then how do they work?
In terms of control theory the answer is very obvious: they supply the
missing damping factor, the differential factor, which is what causes
the mood swings in the first place.
>Some experts such as Bowden (1996) and Keck and McElroy (1996) are so
>concerned about the possibility of rapid cycling that they go still
>further, considering the use of antidepressants as a last resort in
>treating bipolar depression only after multiple mood stabilizers have
>been tried first. While the concern about antidepressants causing rapid
>cycling is based on an indisputable clinical possibility, these experts
>have no illusions about the effectiveness (or indisputable evidence for
>the effectiveness) of anticonvulsant medications as treatment for acute
>bipolar depression. Both valproate and carbamazepine did little better
>than placebo in the studies they cited, but if I understand them
>correctly, they considered bringing relief from the torment of
>depression as quickly as possible a less important priority than not
>iatrogenically causing mood instability.
Exactly. The important features of manic depression to consider here
are that it sometimes seems to wait for some kind of extreme
triggering event, such as the death of a significant other, and that
once the mood swings have been started, they tend, if untreated, not
only to go on, but to get worse. In short, it looks as though extremes
of mood are damaging to the brain, and weaken its resistance to
further swings (the kindling theory). This damage may be only
temporary, and recoverable from, but under the repeated onslaught of
further mood swings there is no chance to recover.
What is being hinted at here, and what it would be unwise (especially
in litigious America) to say too clearly, is that there are grounds
for suspecting that some ordinary depressives with poor mood control
actually get not only pushed into mood swings but pushed into becoming
manic depressives by the use of antidepressants.
>This is not a matter of small significance, since it is not unusual for
>bipolar patients with a predominantly depressive history to be
>exclusively put on mood stabilizers with the expectation that the
>depression will be treated, and that rapid cycling due to the use of
>traditional antidepressants will be avoided. I'm not referring to the
>prophylactic use of mood-stabilizing agents when it is expected that
>antidepressants will later be necessary so that protection against a
>potential manic episode seems judicious. Frequently, mood stabilizers
>are used as the sole antidepressant. Indeed, an expert consensus
>treatment protocol recommends mood stabilizers alone as a first-line
>approach in treating milder major depressive episodes in bipolar I
>disorder and as a second-line approach in bipolar II disorder (Frances
>et al., 1996).
Which is exactly what one should do in order to limit the possibility
of causing manic depression by what one prescribes for depression.
>According to Gary S. Sachs, M.D., the definition of the term mood
>stabilizerdoes not require antidepressant or antimanic efficacy, per se,
>merely that the medication "decrease vulnerability to subsequent
>episodes of mania or depression" and not exacerbate the current episode
>or maintenance phase of treatment (1996).
I'm sure he would have used the term "damper" or "damping factor" had
he been familiar with it, because that is exactly what he is seems to
be struggling to find words for.
>Ariel did have "mood swings." She would be in a perfectly good mood and
>then suddenly, with relatively minor provocation, switch to sadness,
>irritability or an outburst of anger. This was the other major
>justification for placement on a "mood stabilizer." There's only one
>problem with this. The use of the term mood swingsin bipolar disorder
>has usually referred not to labile affect, but to relatively long
>stretches of depression or mania lasting weeks or months-although
>occasionally days-which would then swing to the opposite.
What I have called the "gain" or "amplification" of the system
produces an effect we think of as "stiffness". Think of a very strong
spring. It doesn't move much until you push it very hard. On the other
hand, a very weak spring can be set into wobbling back and forth by
the lightest of touches.
The problem with moods, and mood control, is that these are very basic
elementary ways of getting an animal into the right kind of
behavioural disposition. The ideal way of getting an animal into the
right behavioural dispositions is by the animal understanding what is
going on in an intelligent and rational manner. Unfortunately that
takes a huge brain, somewhat bigger than a human brain. So we have to
make do with moods which make a rough approximation to sensible moods
based on fiddling with the parameters of a multi-level mood control
system. The problem with that kind of mood control system is that
quite different parameters are optimal for different kinds fo
lifestyle, such as peace compared to war. In such circumstances
evolution ensures that there is plenty of variation, so that whatever
the circumstances, there will be some of the right kind of mood
control systems around to handle it well. In short, we should expect
there to be very considerable variation in human mood control systems.
As indeed there is. Much of this variation we call personality. And
one of the parameters to vary is the "stiffness" of the mood control
"spring", i.e., the gain of the system. A system with low gain will
produce exactly this kind of mood lability which Simon Sobo quite
properly distinguishes from "mood swings". In sum, the control theory
model of mood control, and of manic depression, naturally categorises
mood lability as a different kind of thing from the mood swings of the
undamped control system we call manic depression.
Where the line is drawn between lability and mood swing is a question
of the underlying frequency of the system. Any swings at or above that
frequency are artefacts of inadequate damping. Swings below that
frequency are due to inadequate gain.
>Similarly, rapid cycling-defined in the DSM-IV as four or more switches
>in a year-not infrequently appears in clinical summaries when what is
>being described are labile moods.
If the underlying frequency was less than about 2/3 of a year, then
one could get in 3 half oscillations and 4 mood switches. A corollary
of this is that one would never be able to recover from a mood
disturbance due to the natural mood control processes in less than
(2/3)/4 = two months. If research showed that many people have natural
mood recoveries of, say, one month, then this means one month is 1/4
of the natural complete cycle frequency of four months, which in turn
means that a manic depressive could oscillate in mood swings with up
to 9 switches in a year. I would like to suggest on the basis of such
considerations that the DSM-IV definition of "rapid" is far too
conservative, and also not detailed enough, i.e., there should be more
categories.
Of course all this reasoning is based on the simplest possible model of
mood control. There are many extra kinds of complication which could be
present, such as chaotic systems, which often behave like control
systems near the attractors, but which are capable of "mode shifts",
like the heart beat. It is also possible to produce what seems to be a
long cycle period by running two much shorter but slightly "out of
tune" control systems together.
>However, in my experience, high doses
>of selective serotonin reuptake inhibitors seem to work far better for
>labile affect, probably because of their ability to alleviate
>frustration and dull passions rather than from an antidepressant action,
>per se.
This follows as a natural consequence of the fact that (most)
antidepressants seem to work by increasing the gain of the mood
control system. Those which increase the frequency of cycling the most
would be those which increased the gain the most. According to this
control theory model, mood lability (lack of mood "stiffness") is lack
of mood control system gain. So the obvious medication to improve that
will be an antidepressant. The usual therapeutic dose of
antidepressants seem to increase cycling frequency by substantially
less than a factor of two, i.e., they don't double the gain. In the
case of mood lability we want to increase the stiffness a lot, more
than doubling the gain, so we should use very high doses.
It hasn't anything to do with "alleviating frustration and dull
passsions", it follows naturally as a simple consequence of viewing
mood disorders as disorders of mood *control* systems, and viewing
them and the effects of their medications in terms of control theory.
Dr Sobo goes on to suggest that the various anomalies and pradoxes he
describes suggest shifting the terminology of these mood disorders and
their treatment into different kinds of psychological terminology,
e.g., viewing the anti-convulsant mood stabilisers as "exuberance
controllers".
I hope to have suggested that there is a simpler model in terms of the
control theory behind the detailed biochemical kinetics which control
moods, which has more explanatory power than this (or any other) any
other model of manic depression I have seen suggested.
--
Chris Malcolm c...@dai.ed.ac.uk +44 (0)131 650 3085
School of Artificial Intelligence, Division of Informatics
Edinburgh University, 5 Forrest Hill, Edinburgh, EH1 2QL, UK
[http://www.dai.ed.ac.uk/daidb/people/homes/cam/ ] DoD #205
LyndaNP
Hi Chris,
How the heck are you doing? Long time no hear.
Peace,
Lynda