PMS and PMDD: Mood Changes

PMS and PMDD: Mood Changes
During the Menstrual Cycle
FabwNowsolou, MD.
Asdst4,rt Dlrector oJ Clinical Smtices
Women's Mood and Honrume Cltnic, Aniaersity of Califumia, San Fraflcisco
Dr. Novosolov has disclosed that she has no relevant relationships or ftnancial interesm in any
commercial company pertaining to this educational activity.
f all the factors that contribute
to mooa, hormonai vaflauons,
such as those found in premenstrual syndrome (PMS) and premenstrual
dysphoric disorder (PMDD) can have a
paniculady strong efiect. I've heard some
people, for instance, describe PMS as
a "powcrfrrl spell" that women are put
under once every month.
But while it might ftel like a mpterious force to women-and to their significant others-we nowknowmuch more
about its biological basis. And since most
of our patients are women, it's important
for us to be asking about these symp
toIIN, as it can dictate our treatment.
^a^.
I I
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Continuedonpage 2
.
REPORT: PSYCHIATRY
THE '*-CENTAT
-l
-
PMS and PMDDr Mood Changes During the Menstrual Cycle
I
PMDD versus PMS
Continued fmm page
see for a PMDD evaluation come to see
me prompted by their signiffcant other,
with the couple on the verge break-up or
divorce.
So what's the difference between
PMS and PMDD? PMS is very corlmon,
affecting 80% of women with regular
menstrual cydes. These are usually mild
to moderate emotional fluctuations.
When I ask women about premenstrual
symptoms and they shrug it offand tell
me, "I'm a little more moody the week
before my period, but it's not a big deal,"
then it's probably PMS.
PMDD, on the other hand is a severe
form of PMS. The symptoms of PMDD are
similar to those of PMS, but are severe
enough to interfere with wor( social
activities, andlor relationshipe. PMDD
affects3% to 8% of women and feels like
a "hell on earth" period.
The typical story I hear is that for
one to two weeks before menses, a
woman's life is dramatically derailed:
fights with her signiffcant other, missing
work or school, suicidal thoughts. Then,
right when her period starts, these symP
toms are suddenly lifted and she feels
"great" again. ln fact, a lot of women I
EDNORIALINFORMAIION
.
ord CEO: Stere Zlsem
Edttor-in-Cbtef Stcve BaA, MD, is a psychiauist
in pri te pfactice in dle San franclsco Bay atea
P?esideflt
AMate Edrm
ilxtigl.
Zucterma, I{D,
.
director of fychlealc Serrke at Valden Beharioral
Caein\traldum, MA
Ewantriw Edltor: Amy
Edttorial Board:
Hding, iIA
Ronald C Alhldt€tr, MD, director of counsel-
ing and poychologicrl services, alinical associae
professoi of psychiauy, Sanford Univenity, Palo
Alto, CA
Rictrud Gardiner, MD, psychiatrist in private
practice in Poner Valley, CA
Alan D. Lyman, lID, child and adolesceot psychiatrist in private practice, New York City, NY
Jemes Megnz, MD, PhD, director of inpatient
psychiatry, associate professor of psyc-hiatry and
medicine at SUNY Upstate Medical University,
Syracuse, NY
Robert L Mlck, MD, contract physLian in
addiction medkine and.miliary.psyclhtrl
Bloomfield, NY.
Itltclr.el Postemik, ilD, psychiatrht in prh/rte
practice, Boston, MA
Glen Spietmans, PhD, associate proftssor of
psychology, Metropolitan State Unir€rsity, St. Paul,
ia
,
MN
Alt editorial conrcnt is peer rwiewed by the
editorial board: Dr. Albucher, fu. Gadiner, Dr.
tyma& Dr. Megn4.Dr Mict, Dr. Postemat Dr.
Spiekoars fld Dr:Zuckerrnan hayp disclased that
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Ameiicl. This CME&E.activity is intetded for
p65.cli't ttists,.psycbiatric nurse6, pgychologisa
and O&er healt[,ic4B lr-foftssiooals widi an inter'
esrin the.&agoil$rdiiil.neatment of psychiatric
Diagnostic Criteria for PMDD
PMDD involves severe mood swings,
depressed mood, irritability or anxiety,
and four other emotional or physical
symptoms occurring exclusively during
the luteal phase (the one to two weets
before menses) and lifting within a few
days of the onset of menses. To meet the
PMDD diagnostic criteria, the symptoms
must cause clinically significant distress
or interfere with work, school, usual
social activities, or relationships.
PMDD was made an official diagnosis
in DSM-S in 2013. Although diagnostic
criteria may look complicated and over'
whelming, I find it helpful to think of
PMDD as a woflun meeting criteria for a
MDE (mafor depressive episode) one to
two weeLs before menses (with or with'
out physical symptoms like breast tender'
ness, cramps, or bloating), but then feeling 100% normal the other two or three
week.
Pathophysiolog;y
So what is going on here? There's
good evidence that biology plays a key
role. For starters, more women are
admitted to psychiaric hospitals in the
week immediately prior to menses than
on any other week In one study, 47% of
admissions occurred during this week
(Targum SD etal,J $ea Disorders
rWt;22(1-2):4Y53).
Before going fufther, it helps to
understand basic biology. In the first half
of the menstrual cycle, a follide grows
into an egg (hence the tetmfollicular
pbase fot this part ofthe cycle). Then,
after 14 days, the egg is released (ovula'
tion). What is left behind is a structurc
called the corpus luteum (hence the term
luteal pbase), which then starts producing progesterone to thicken the uterine
lining to prepare for implantation.
If the egg is not fertilized, then the
corpus luteum stops secreting progester'
one and decays. Thus, there is a drop in
pfogesterione one to two weets before
menses, and this drop is what triggers
the uterine lining to shed (menstrua'
tion). Recent research suggests that some
women ane more sensitive than others to
this fall in progesterone, and this sensitiyity causes the mood symptoms of PMDD.
A groundbreaking 1999 study found
that progesterone gets converted into
another homone called allopregnano
lone, which binds the GABA-A recep
tor-the szrme receptor to which benzodiazepines and alcohol bind-and acs
as a powerful anxiolytic, anticonv-ul$ant,
and anesthetic agent that decreases
anxiety and depression (Griffin t and
Mellon S, Proceedings Nml Acad Sci USA
rW;96(23):13512-7).
Think ofallopregnanolone
as a
soothing, calming hormone. When the
progesterone levef drops, the allopregaanolone level also falls. For women who
are sensitive to this drop, it's similar to
experiencing diazepari (Valium) or alco.
holwithdrawal.
You might be tempted to measure
levels of progesterone or allopregrrano
lone, but such tesa pmbably wouldn't
tell you very much. They would most
likely be normal, as would the rate of the
progesterone or allopregnanolone drop
during the luteal phase. PMDD is a clinical diagrrosis and the current hypothesis
is that it has to do with a woman's sensitivity to this drop in hormone$-not to
abnormal hormone levels themsehes.
Treatment
SSRIs. So what can we do about
PMDD?We all know the SSRI's mecha'
nism ofaction related to the increase in
receptor sensitivity to serotonin after four
to six weeks. But it tums out that a sec'
ond mechanism of action involves helping to accelerate the conversion ofpro
gesterone to allopregnanolone. Research
has found that fluoxetine, sertraline, and
pafoxetine decrease the,l(. (energy of
activation needed for the reaction) of the
enzqe lG to 3Gfold (Gnffinibid).
This means that progesterone is con
verted much hster into allopregnanolone
and there is'more of it around to act on
GABA receptors. Imipramine (a tricyclic
antidepressant) appears to have no such
effect, and this effect seems to be specific
to
SSRIs alone.
Amazing$, this second mechanism of
action works quickly, often within several
dap. In fact, many of my patients tell me
Cantinued onpage 3
THE CEnTAT REPORT: PSYCHIATRY
PMS and PMDD Mood Changes During the Mensrual Cycle
Continued lrem page 2
that their symptoms completely go away
within hours of taking an SSRI. Typically,
only a low dose SSRI is needed (fluoxetine 10 to 20 mg daih or sertraline 25 to
50 mg daily, for example).
The SSRI can be started seven to 10
days prior to menses (or whenever your
patient's PMDD symptoms come on), or
daily if the worun is also depressed or
anxious atbaseline on the other days. Or,
if there is baseline depression or arxiety that is exace6ated the week beiore
menses each month, the SSRI dose can
be increased fust during the week before
menses.
This is an important distinction: if a
woman doesn't return to baseline during the other two to three weeks of the
month, it's not true PMDD and would be
considered premenstrual exacerbation
(PME). I often record this as MDD with
PME, or GAD with PME, for example.
Some women really like the idea of
intennittent dosing, especially if they are
weary of side effecs. Surprisingly, I have
never seen withdrawal or discontinuation
symptoms with intermittent dosing, likely
due to the low doses needed for PMDD.
Hotmanas. Another possible treatment is hormones, specifically oral
contraceptive pills (OCP$. OCPs work
by "flattening out" the body's hormone
levels (keeping the levels consistent without any peals or uoughs), as the puient
takes the exact same dose of progesterone and estrogen daily.
Some women are fine with the
standard placebo week (the week in
which the daily pill contains no active
hormone), while others get a mood drop
shifted to the placebo week when there
is a drop in hormones. These women
do best by uking the active pill continuously and cuuing out the placebo week
altogether.
It is also important to mention that
women are sensitive to hormones in different ways-some to the hormone fluctuation, some to the amount, and others
to the specific progestin type. Therefore,
you might have to try a few difierent
OCPs. \ffomen who are sensitive to hormonal fluctuations should avoid triphasic
OCPs. It usually takes about two cydes to
see if an OCP will work.
The combination drospirenone/
ethinyt estradiol (Yaz), the only OCP
studied for PMDD, has shown good
results for both physical and mood symp
toms (Yonkers KA et d, Obstet Gjmccol
2A05lM492-50f). It shortens the placebo week to four days instead of the usual
seven, which, in practice, could be done
with any OCP. Keep in mind *rat OCPs,
like SSRIs, can lower libido<specially
Yaz, since the progestin it uses (drospirenone) has antiandrogenic activity.
I am often asked what it is better to
tryfirst,
SSRIs
or
OCPs?
It depends on
the individual. Women who don't like
the idea of hormones or have a history
of worsening mood with OCPs might
prefer SSRIs, while women who aren't
keen about taking psychiatric medications might wish to try OCPs first. In my
practice, I have found that it's usually
easier to start with ao SSRI since you
know pretty much immediately if it will
work or not.
Benzndtoze?dzes. As you might
imagine, benzodiazepines can also be
an effective treatment for PMDD or PME
since they work on the GABA recep
tor. Sometimes I'll give patients a smdl
amount of both fluoxetine and lorazepam
(Atiran), br orample, and ask them to
try both during their premenstrual week
to see which is more effective for them
(Freeman E et al, Prim Care Cornpanion
J C lin P qtcbiatry 2a03 ;5 (L) :30-39).
Qtb er anttdelm ssents. Although
SSRIs are the gold standard for PMDD,
there has been some evidence that
serotonin-norepinephrine reuptake
inhibitors (SNRIs) and clomipramine (a
tricyclic antidepressant) show some efficacy
for PMDD (see, for instance, Mazza
M et al, Expert Optn Pbarmacotber
2N8;9(4)St7-52t).
Non-pb am,rcologbal tte aments.
a woman
through the pathophysiology of PMDD or
PME so that she and her hmily are more
aware of the biological erylanation of
her symptoms. I often have women nzck
their symptoms on a mood chan for at
least two months. This serves two functions: (1) it can ensurc that we are dealing with a premenstrual pattem, and (2)
it can often help decrease distress by p.edicting when the bad days are coming.
Although there is no consensus
about the best tracking tools, two wellvalidated scales include tJre Cdendar of
It can be helpful to simply walk
Premenstrual Experiences (COPE) and
the Prospective Record ofthe Severityof
Menstruation (PRISM), both of which ask
the patient to measure a variety of symp'
toms on each day of her cyde.
Other helpful things to try are diet
and lifestyle changes: eliminating caffeine, sug;ar and sodium use, cutting out
nicotine and alcohol use, getting good
sleep and regular exercise (for more
information, see http:/Ait.lyl$rg1i9.
In terms ofpsychotherapy, one study
found that cognitive-behavioral therapy
(CBT) was as effective as fluoxetine (20
mg daily) in the treatment of women
with PMDD at the end of six months,
as measured by a prospective daily
diary (flunter MS et al,J Pqtcboson Res
2002;53(3):8t1-817).
Cenain nutritional supplements have
also shown promise in various studies
for pfunical and emotional symptoms
of PMDD, induding calcium (1,200 mg/
day) and Vitamin 85 (50 to 100 mg/day).
Make sure to caution patients that Vitamin 86 in doses above 100 mg/day can
peripherd neuropatiy. There is
also some limited evidence that megne-
cause
sium (2fi) to360mg/day) andVitamin E
(4O0 lu/day) can provide modest relief of
slmptoms.
Herbal remedies may also be helpful.
Placebocontrolled studies have shown
that exracts af.Agnus casfas fruit, also
known as chasteberry, can significandy
decrease emotional and phpical PMS
symptoms, and that Gingrta biloba cm
also improve symptoms of PMS.
Ught therapy has also been explored
as a possible treatment for PMDD (see
htlpt//bit.lyryrglN). More work must be
done to determine optimal doses and
treatment durations for these alternatirr
interventions.
LED
Mood changes are common
during the mensmral
ru^ffiffi:s*fliffi:,
thmughout
the
and their metabolites
cycle. PMDD may result hom sensitivityto rapid changes in estrogen and
pr€{iesterone levels:, Oral contraceP
tives, &SRIs, and other interventions can
be effective tneatnents.