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Penatalaksanaan Gangguan Bipolar

Suasana alam perasaan (mood) bervariasi, bisa normal, menurun ataupun meningkat dan individu dapat
mengkontrol suasana alam perasaannya.
Bila terjadi gangguan dalam alam perasaan , individu kehilangan kontrol terhadap perasaannya tersebut dan
timbullah penderitaan.
Penderita dengan mood yang meningkat menunjukkan expansiveness, flight of ideas, penurunan tidur,
peningkatan self esteem, serta ide ide kebesaran.
Penderita dengan mood terdepresi kehilnagan minat dan energi, merasakan perasaan bersalah, sulit
berkonsentrasi, kehilangan nafsu makan, sert amempunyai ide ide kematian bahkan bunuh diri.
Gejala lain adalah perubahan dalam tingkatan aktivitas, kemampuan kognitif, kemampuan biara dan
Perubahan perubahan tersebut selalu menimbulkan gangguna dalam hubungan interpersonal, sosial dan
fungsi okupasi.
Prevalensi gangguan ini berkisar antara "#"$%
&ingga saat ini belum diketahui etiologi yang pasti.
'()* Gangguan +fektif Bipolar
,anifestasi -linis
.itandai dengan episode berulang sekurangnya dua
'()./ Gangguna +fektif Bipolar , !pisode -ini &ipomanik
'().) Gangguan +fektif Bipolar, !pisode
'()." Gangguan +fektif Bipolar , !pisode -ini ,anik .engan Gejala Psikotik*
'().( Gangguan +fektif Bipolar, !pisode -ini .epresi 0ingan atau Sedang*
'().1 G+ngguan +fektif Bipolar, !pisode -ini .epresi Berat 2anpa Gejala Psikotik
'().$ Gangguan +fektif Bipolar, !pisode -ini .epresi Berat dengan Gejala Psikotik
'().3 Gangguan +fektif Bipolar, !pisode -ini 4ampuran
'().5 Gangguan +fektif Bipolar , -ini dalam 0emisi
'().6 Gangguan +fektif Bipolar 7ainnya,
'().8 Gangguan +fektif Bipolar 922*
Gangguan +fektif Bipolar .an Gangguan .epresi
&arus memenuhi kriteria*
). :aminan keamanan pasien
". !valuasi diagnosis yang lengkap
(. 0enana terapi jangka pendek dan jangka panjang
2reatment of patients ;ith mood disorders should be direted to;ard several goals. 'irst,
the patient<s safety must be guaranteed. Seond, a omplete diagnosti evaluation of the
patient is neessary. 2hird, a treatment plan that addresses not only the immediate
symptoms but also the patient<s prospetive ;ell#being should be initiated. +lthough
urrent treatment emphasi=es pharmaotherapy and psyhotherapy addressed to the
individual patient, stressful life events are also assoiated ;ith inreases in relapse rates.
2hus, treatment should address the number and severity of stressors in patients< lives.
>verall, the treatment of mood disorders is re;arding for psyhiatrists. Speifi
treatments are no; available for both mani and depressive episodes, and data indiate
that prophylati treatment is also effetive. Beause the prognosis for eah episode is
good, optimism is al;ays ;arranted and is ;elomed by both the patient and the patient<s
family. ,ood disorders are hroni, ho;ever, and the psyhiatrist must eduate the
patient and the family about future treatment strategies.
2he first and most ritial deision a physiian must make is ;hether to hospitali=e a
patient or attempt outpatient treatment. 4lear indiations for hospitali=ation are the risk of
suiide or homiide, a patient<s grossly redued ability to get food and shelter, and the
need for diagnosti proedures. + history of rapidly progressing symptoms and the
rupture of a patient<s usual support systems are also indiations for hospitali=ation.
+ physiian may safely treat mild depression or hypomania in the offie if he or she
evaluates the patient fre?uently. 4linial signs of impaired judgment, ;eight loss, or
insomnia should be minimal. 2he patient<s support system should be strong, neither
overinvolved nor ;ithdra;ing from the patient. +ny adverse hanges in the patient<s
symptoms or behavior or the attitude of the patient<s support system may suffie to
;arrant hospitali=ation.
2able )$.)#() ,ajor 'eatures of 2hree Psyhotherapeuti +pproahes to .epression
'eature Psyhodynami
4ognitive +pproah @nterpersonal
,ajor theorists 'reud, +braham,
:aobson, -ohut
Plato, +dler, Bek,
,eyer, Sullivan,
-lerman, Aeissman
4onepts of
pathology and ause
!go regression*
damaged self#
esteem and
unresolved onflit
due to hildhood
objet loss and
.istorted thinking*
dysphoria due to
learned negative
vie;s of self, others,
and the ;orld
relations* absent or
signifiant soial
,ajor goals and
mehanisms of
2o promote
personality hange
understanding of
past onflitsB to
ahieve insight into
defenses, ego
distortions, and
superego defetsB to
provide a role
modelB to permit
atharti release of
2o provide
symptomati relief
through alteration of
target thoughtsB to
identify self#
ognitionsB to
modify speifi
assumptionsB to
promote self#ontrol
over thinking
2o provide
symptomati relief
through solution of
urrent interpersonal
problemsB to redue
stress involving
family or ;orkB to
Primary tehni?ues
and praties
empathi* fully or
partially analy=ing
transferene and
ognitive* reording
and monitoring
larifying and
defensesB larifying
ego and superego
orreting distorted
themes ;ith logi
and experimental
testingB providing
alternative thought
ontentB home;ork
relationships and
learning ne; ones
ommuniation and
soial skills trainingB
information on
2herapist role#
establishment and
exploration of
therapeuti alliane
for benign
dependene and
positive relationship
instead of
empiriism as basis
for joint sientifi
(logial) task
transferene ;ithout
interpretationB ative
therapist role for
influene and
,arital#family role 'ull individual
exlusion of
signifiant others
exept in life#
Cse of spouse as
objetive reporterB
ouples therapy for
disturbed ognitions
sustained in marital
@ntegral role of
spouse in treatmentB
examination of
spouse<s role in
predisposition to
depression and
effets of illness on
('rom -arasu 2B. 2o;ard a linial model of psyhotherapy for depression. @.
Systemati omparison of three psyhotherapies. Am J Psychiatry. )88/B)15*)1), ;ith
Patients ;ith mood disorders are often un;illing to enter a hospital voluntarily, and may
have to be involuntarily ommitted. 2hese patients often annot make deisions beause
of their slo;ed thinking, negative Aeltanshauung (;orld vie;), and hopelessness.
Patients ;ho are mani often have suh a omplete lak of insight into their disorder that
hospitali=ation seems absolutely absurd to them.
Psyhosoial 2herapy
+lthough most studies indiateDEFand most liniians and researhers believeDEFthat a
ombination of psyhotherapy and pharmaotherapy is the most effetive treatment for
major depressive disorder, some data suggest another vie;* !ither pharmaotherapy or
psyhotherapy alone is effetive, at least in patients ;ith mild major depressive episodes,
and the regular use of ombined therapy adds to the ost of treatment and exposes
patients to unneessary adverse effets.
2hree types of short#term psyhotherapiesDEFognitive therapy, interpersonal therapy,
and behavior therapyDEFhave been studied to determine their effiay in the treatment of
major depressive disorder. +lthough its effiay in treating major depressive disorder is
not as ;ell researhed as these three therapies, psyhoanalytially oriented psyhotherapy
has long been used for depressive disorders, and many liniians use the tehni?ue as
their primary method. Ahat differentiates the three short#term psyhotherapy methods
from the psyhoanalytially oriented approah are the ative and diretive roles of the
therapist, the diretly reogni=able goals, and the end points for short#term therapy.
+umulating evidene is enouraging about the effiay of dynami therapy. @n a
randomi=ed, ontrolled trial omparing psyhodynami therapy ;ith ognitive behavior
therapy, the outome of the depressed patients ;as the same in the t;o treatments.
2able )$.)#() summari=es the features of the psyhodynami, ognitive, and
interpersonal approahesB 2able )$.)#(" summari=es some nonseletive and seletive
patient variables for psyhotherapyB 2able )$.)#(( summari=es the advantages and
limitations of the three approahesB and 2ables )$.)#(1,)$.)#($ summari=e features that
may affet the hoie of pharmaotherapy or psyhotherapy or ombined therapy. 2he
Gational @nstitute of ,ental &ealth (G@,&) 2reatment of .epression 4ollaborative
0esearh Program found the follo;ing preditors of response to various treatments* lo;
soial dysfuntion suggested a good response to interpersonal therapyB lo; ognitive
dysfuntion suggested a good response to ognitive#behavioral therapy and
pharmaotherapyB high ;ork dysfuntion suggested a good response to pharmaotherapyB
and high depression severity suggested a good response to interpersonal therapy and
4ognitive 2herapy
4ognitive therapy, originally developed by +aron Bek, fouses on the ognitive
distortions postulated to be present in major depressive disorder. Suh distortions inlude
seletive attention to the negative aspets of irumstanes and unrealistially morbid
inferenes about onse?uenes. 'or example, apathy and lo; energy result from a
patient<s expetation of failure in all areas. 2he goal of ognitive therapy is to alleviate
depressive episodes and prevent their reurrene by helping patients identify and test
negative ognitionsB develop alternative, flexible, and positive ;ays of thinkingB and
rehearse ne; ognitive and behavioral responses.
Studies have sho;n that ognitive therapy is effetive in the treatment of major
depressive disorder. ,ost studies found that ognitive therapy is e?ual in effiay to
pharmaotherapy and is assoiated ;ith fe;er adverse effets and better follo;#up than
pharmaotherapy. Some of the best ontrolled studies have indiated that the ombination
of ognitive therapy and pharmaotherapy is more effiaious than either therapy alone,
although other studies have not found that additive effet. +t least one study, the G@,&
2reatment of .epression 4ollaborative 0esearh Program, found that pharmaotherapy,
either alone or ;ith psyhotherapy, may be the treatment of hoie for patients ;ith
severe major depressive episodes.
@nterpersonal 2herapy
@nterpersonal therapy, developed by Gerald -lerman, fouses on one or t;o of a patient<s
urrent interpersonal problems. 2his therapy is based on t;o assumptions. 'irst, urrent
interpersonal problems are likely to have their roots in early dysfuntional relationships.
Seond, urrent interpersonal problems are likely to be involved in preipitating or
perpetuating the urrent depressive symptoms. 4ontrolled trials have indiated that
interpersonal therapy is effetive in the treatment of major depressive disorder and, not
surprisingly, may be speifially helpful in addressing interpersonal problems. Some
studies indiate that interpersonal therapy may be the most effetive method for severe
major depressive episodes ;hen the treatment hoie is psyhotherapy alone.
2he interpersonal therapy program usually onsists of )" to )3 ;eekly sessions and is
harateri=ed by an ative therapeuti approah. @ntrapsyhi phenomena, suh as
defense mehanisms and internal onflits, are not addressed. .isrete behaviorsDEFsuh
as lak of assertiveness, impaired soial skills, and distorted thinkingDEFmay be
addressed but only in the ontext of their meaning in, or their effet on, interpersonal
Behavior 2herapy
Behavior therapy is based on the hypothesis that maladaptive behavioral patterns result in
a person<s reeiving little positive feedbak and perhaps outright rejetion from soiety.
By addressing maladaptive behaviors in therapy, patients learn to funtion in the ;orld in
suh a ;ay that they reeive positive reinforement. Behavior therapy for major
depressive disorder has not yet been the subjet of many ontrolled studies. 2he limited
data indiate that it is an effetive treatment for major depressive disorder.
Psyhoanalytially >riented 2herapy
2he psyhoanalyti approah to mood disorders is based on psyhoanalyti theories about
depression and mania. 2he goal of psyhoanalyti
psyhotherapy is to effet a hange in a patient<s personality struture or harater, not
simply to alleviate symptoms. @mprovements in interpersonal trust, apaity for intimay,
oping mehanisms, the apaity to grieve, and the ability to experiene a ;ide range of
emotions are some of the aims of psyhoanalyti therapy. 2reatment often re?uires the
patient to experiene periods of heightened anxiety and distress during the ourse of
therapy, ;hih may ontinue for several years.
'amily 2herapy
'amily therapy is not generally vie;ed as a primary therapy for the treatment of major
depressive disorder, but inreasing evidene indiates that helping a patient ;ith a mood
disorder to redue and ope ;ith stress an lessen the hane of a relapse. 'amily therapy
is indiated if the disorder jeopardi=es a patient<s marriage or family funtioning or if the
mood disorder is promoted or maintained by the family situation. 'amily therapy
examines the role of the mood#disordered member in the overall psyhologial ;ell#
being of the ;hole familyB it also examines the role of the entire family in the
maintenane of the patient<s symptoms. Patients ;ith mood disorders have a high rate of
divore, and about $/ perent of all spouses report that they ;ould not have married or
had hildren if they had kno;n that the patient ;as going to develop a mood disorder.
Hagal Gerve Stimulation
!xperimental stimulation of the vagus nerve in several studies designed for the treatment
of epilepsy found that patients sho;ed improved mood. 2his observation led to the use of
left vagal nerve stimulation (HGS) using an eletroni devie implanted in the skin,
similar to a ardia paemaker. Preliminary studies have sho;n that a number of patients
;ith hroni,
reurrent major depressive disorder ;ent into remission ;hen treated ;ith HGS. 2he
mehanism of ation of HGS to aount for improvement is unkno;n. 2he vagus nerve
onnets to the enteri nervous system and, ;hen stimulated, may ause release of
peptides that at as neurotransmitters. !xtensive linial trials are being onduted to
determine the effiay of HGS. Setion (3.(5 overs this and other brain stimulation
Sleep .eprivation
,ood disorders are harateri=ed by sleep disturbane. ,ania tends to be harateri=ed
by a dereased need for sleep, ;hereas depression an be assoiated ;ith either
hypersomnia or insomnia. Sleep deprivation may preipitate mania in patients ;ho are
bipolar @ and temporarily relieve depression in those ;ho are unipolar. +pproximately 3/
perent of depressive disorder patients exhibit signifiant but transient benefit from total
sleep deprivation. 2he positive results are typially reversed by the next night of sleep.
Several strategies have been used in an attempt to ahieve a more sustained response to
sleep deprivation. >ne method used serial total sleep deprivation ;ith a day or t;o of
normal sleep in bet;een. 2his method does not ahieve a sustained antidepressant
response beause the depression tends to return ;ith normal sleep yles. +nother
approah used phase delay in the time patients go to sleep eah night, or partial sleep
deprivation. @n this method, patients may stay a;ake from " +, to )/ P, daily. Cp to
$/ perent of patients get same#day antidepressant effets from partial sleep deprivation,
but this benefit also tends to ;ear off in time. @n some reports, ho;ever, serial partial
sleep deprivation has been used suessfully to treat insomnia assoiated ;ith depression.
2he third, and probably most effetive, strategy ombines sleep deprivation ;ith
pharmaologial treatment of depression. + number of studies have suggested that total
and partial sleep deprivation follo;ed by immediate treatment ;ith an antidepressant or
lithium (!skalith) sustains the antidepressant effets of sleep deprivation. 7ike;ise,
several reports have suggested that sleep deprivation aelerates the response to
antidepressants, inluding fluoxetine (Pro=a) and nortriptyline (+ventyl, Pamelor). Sleep
deprivation has also been noted to improve premenstrual dysphoria.
Phototherapy (light therapy) ;as introdued in )861 as a treatment for S+. (mood
disorder ;ith seasonal pattern). @n this disorder, patients typially experiene depression
as the photoperiod of the day dereases ;ith advaning ;inter. Aomen represent at least
5$ perent of all patients ;ith seasonal depression, and the mean age of presentation is
1/. Patients rarely present over the age of $$ ;ith seasonal affetive disorder.
Phototherapy typially involves exposing the afflited patient to bright light in the range
of ),$// to )/,/// lux or more, typially ;ith a light box that sits on a table or desk.
Patients sit in front of the box for approximately ) to " hours before da;n eah day,
although some patients may also benefit from exposure after dusk. +lternatively, some
manufaturers have developed light visors, ;ith a light soure built into the brim of the
hat. 2hese light visors allo; mobility, but reent ontrolled studies have ?uestioned the
use of this type of light exposure. 2rials have typially lasted ) ;eek, but longer
treatment durations may be assoiated ;ith greater response.
Phototherapy tends to be ;ell tolerated. Ge;er light soures tend to use lo;er light
intensities and ome e?uipped ;ith filtersB patients are instruted not to look diretly at
the light soure. +s ;ith any effetive antidepressant, phototherapy, on rare oasions,
has been impliated in s;ithing some depressed patients into mania or hypomania.
@n addition to seasonal depression, the other major indiation for phototherapy may be in
sleep disorders. Phototherapy has been used to derease the irritability and diminished
funtioning assoiated ;ith shift ;ork. Sleep disorders in geriatri patients have
reportedly improved ;ith exposure to bright light during the day. 7ike;ise, some
evidene suggests that jet lag might respond to light therapy. Preliminary data indiate
that phototherapy may benefit some patients ;ith >4. that has a seasonal variation.
>ne a diagnosis has been established, a pharmaologial treatment strategy an be
formulated. +urate diagnosis is ruial, beause unipolar and bipolar spetrum
disorders re?uire different treatment regimens.
2he objetive of pharmaologi treatment is symptom remission, not just symptom
redution. Patients ;ith residual symptoms, as opposed to full remission, are more likely
to experiene a relapse or reurrene of mood episodes and to experiene ongoing
impairment of daily funtioning.
,ajor .epressive .isorder
2he use of speifi pharmaotherapy approximately doubles the hanes that a depressed
patient ;ill reover in ) month. +ll urrently available antidepressants may take up to (
to 1 ;eeks to exert signifiant therapeuti effets, although they may begin to sho; their
effets earlier. 4hoie of antidepressants is determined by the side effet profile least
objetionable to a given patient<s physial status, temperament, and lifestyle. 2hat
numerous lasses of antidepressants (2able )$.)#(3) are available, many ;ith different
mehanisms of ation, represents indiret evidene for heterogeneity of putative
biohemial lesions. +lthough the first antidepressant drugs, the monoamine oxidase
inhibitors (,+>@s) and triyli antidepressants (24+s), are still in use, ne;er
ompounds have made the treatment of depression more DEIliniian and patient
General 4linial Guidelines
2he most ommon linial mistake leading to an unsuessful trial of an antidepressant
drug is the use of too lo; a dosage for too short a time. Cnless adverse events prevent it,
the dosage of an antidepressant should be raised to the maximum reommended level and
maintained at that level for at least 1 or $ ;eeks before a drug trial is onsidered
unsuessful. +lternatively, if a patient is improving linially on a lo; dosage of the
drug, this dosage should not be raised unless linial improvement stops before maximal
benefit is obtained. Ahen a patient does not begin to respond to appropriate dosages of a
drug after " or ( ;eeks, liniians may deide to obtain a plasma onentration of the
drug if the test is available for the partiular drug being used. 2he test may indiate either
nonompliane or partiularly unusual pharmaokineti disposition of the drug and may
thereby suggest an alternative dosage.
2able )$.)#(3 +ntidepressant ,ediations
Common Side
Effects Clinical Caveats
NE Reuptake n!i"itors
5$DEK(// .ro;siness,
insomnia, >S&,
agitation, 4+, ;eight
DLM, antiholinergi
>verdose may be fatal. .ose titration is
"/DEK3/ .ro;siness,
insomnia, >S&,
agitation, 4+,
>verdose may be fatal. .ose titration is
1/DEK"// .ro;siness, >S&,
4+, ;eight DLM,
>verdose may be fatal. .ose titration is
.ro;siness, 4+,
;eight DLM,
>verdose may be fatal. .ose titration is
#$%& Reuptake n!i"itors
"/DEK3/ +ll SS0@s may ause
insomnia, agitation,
sedation, G@ distress,
and sexual
,any SS0@s inhibit various ytohrome
P1$/ isoen=ymes. 2hey are better tolerated
than triylis and have high safety in
overdose. Shorter half#life SS0@s may be
assoiated ;ith disontinuation symptoms
;hen abruptly stopped.
e (Pro=a)
e (Paxil)
NE and #$%& Reuptake n!i"itors
5$DEK(// .ro;siness, >S&,
4+, ;eight DLM,
>verdose may be fatal. .ose titration is
5$DEK(// .ro;siness, >S&,
4+, ;eight DLM,
>verdose may be fatal.
5$DEK(// .ro;siness,
insomnia and
agitation, >S&, 4+,
G@ distress, ;eight
DLM, antiholinergi
>verdose may be fatal. .ose titration
5$DEK(// .ro;siness, >S&,
4+, ;eight DLM,
Sleep hanges, G@
&igher doses may ause hypertension. .ose
titration is needed. +brupt disontinuation
may result in disontinuation symptoms.
(/DEK3/ G@ distress,
're$ and 'ostsynaptic (ctive (gents
Sedation .ose titration is needed. Go sexual
)$DEK(/ Sedation, ;eight DLM Go sexual dysfuntion.
Dopamine Reuptake n!i"itor
@nsomnia or agitation,
G@ distress
2;ie#a#day dosing ;ith sustained release.
Go sexual dysfuntion or ;eight gain.
)i*ed (ction (gents
4+, ;eight DLM,
>S&, antiholinergi
,ovement disorders may our. .ose
titration is needed.
5$DEK(// .ro;siness, ;eight
.ose titration is needed.
.ro;siness, >S&,
4+, G@ distress,
;eight DLM
Priapism is possible.
Note* .ose ranges are for adults in good general medial health, taking no other mediations,
aged )6 to 3/ years. .oses vary depending on the agent, onomitant mediations, the
presene of general medial or surgial onditions, age, geneti onstitution, and other fators.
Brand names are those used in the Cnited States.
4+, ardia arrhythmiaB $#&2, serotoninB G@, gastrointestinalB G!, norepinephrineB >S&,
orthostati hypotensionB SS0@, seletive serotonin reuptake inhibitor.
.ry mouth, blurred vision, urinary hesitany, and onstipation.
Got approved as an antidepressant in the Cnited States by the CS 'ood and .rug
.uration and Prophylaxis
+ntidepressant treatment should be maintained for at least 3 months or the length of a
previous episode, ;hihever is greater. Prophylati treatment ;ith antidepressants is
effetive in reduing the number and severity of reurrenes. >ne study onluded that
;hen episodes are less than "PQ years apart, prophylati treatment for $ years is
probably indiated. +nother fator suggesting prophylati treatment is the seriousness of
previous depressive episodes. !pisodes that have involved signifiant suiidal ideation or
impairment of psyhosoial funtioning may indiate that liniians should onsider
prophylati treatment. Ahen antidepressant treatment is stopped, the drug dose should
be tapered gradually over ) to " ;eeks, depending on the half#life of the partiular
ompound. Several studies indiate that maintenane antidepressant mediation appears
to be safe and effetive for the treatment of hroni depression.
Prevention of ne; mood episodes (i.e., reurrenes) is the aim of the maintenane phase
of treatment. >nly those patients ;ith reurrent or hroni depressions are andidates for
maintenane treatment.
@nitial ,ediation Seletion
2he available antidepressants do not differ in overall effiay, speed of response, or long#
term effetiveness. +ntidepressants, ho;ever, do differ in their pharmaology,
drugDEKdrug interations, short# and long#term side effets, likelihood of disontinuation
symptoms, and ease of dose adjustment. 'ailure to tolerate or to respond to one
mediation does not imply that other mediations ;ill also fail. Seletion of the initial
treatment depends on the hroniity of the ondition, ourse of illness (a reurrent or
hroni ourse is assoiated ;ith inreased likelihood of subse?uent depressive
symptoms ;ithout treatment), family history of illness and treatment response, symptom
severity, onurrent general medial or other psyhiatri onditions, prior treatment
responses to other aute phase treatments, potential drugDEKdrug interations, and patient
preferene. @n general, approximately 1$ to 3/ perent of all outpatients ;ith
unompliated (i.e., minimal psyhiatri and general medial omorbidity), nonhroni,
nonpsyhoti major depressive disorder ;ho begin treatment ;ith mediation respond
(i.e., ahieve at least a $/ perent redution in baseline symptoms)B ho;ever, only ($ to
$/ perent ahieve remission (i.e., the virtual absene of depressive symptoms).
2reatment of .epressive Subtypes
4linial types of major depressive episodes may have varying responses to partiular
antidepressants, or to drugs other than antidepressants. Patients ;ith major depressive
disorder ;ith atypial features (sometimes alled hysteriod dysphoria) may preferentially
respond to treatment ;ith ,+>@s or SS0@s. +ntidepressants ;ith dual ation on both
serotonergi and noradrenergi reeptors demonstrate greater effiay in melanholi
depressions. Patients ;ith seasonal ;inter depression an be treated ;ith light therapy.
2reatment of major depressive episodes ;ith psyhoti features may re?uire a
ombination of an antidepressant and an atypial antipsyhoti. Several studies have also
sho;n that !42 is effetive for this indiationDEFperhaps more effetive than
pharmaotherapy. 'or those ;ith atypial symptom features, strong evidene exists for
the effetiveness of ,+>@s. SS0@s and bupropion (Aellbutrin) are also of use in atypial
4omorbid .isorders
2he onurrent presene of another disorder an affet initial treatment seletion. 'or
example, the suessful treatment of >4. assoiated ;ith depressive symptoms usually
results in remission of the depression. Similarly, ;hen pani disorder ours ;ith major
depression, mediations ;ith demonstrated effiay in both onditions are preferred (e.g.,
triylis and SS0@s). @n general, the nonmood disorder ditates the hoie of treatment in
omorbid states.
4onurrent substane abuse raises the possibility of a substane#indued mood disorder,
;hih must be evaluated by history or by re?uiring abstinene for several ;eeks.
+bstinene often results in remission of depressive symptoms in substane#indued mood
disorders. 'or those ;ith ontinuing signifiant depressive symptoms, even ;ith
abstinene, an independent mood disorder is diagnosed and treated.
General medial onditions are established risk fators in the development of depression.
2he presene of a major depressive episode is assoiated ;ith inreased morbidity or
mortality of many general medial onditions (e.g., ardiovasular disease, diabetes,
erebrovasular disease, and aner).
2herapeuti Cse of Side !ffets
4hoosing more sedating antidepressants (e.g., amitriptyline R!lavil, !ndepS) for more
anxious, depressed patients or more ativating agents (e.g., desipramine) for more
psyhomotor#retarded patients is not generally helpful. 'or example, any short#term
benefits ;ith paroxetine, mirta=apine, or amitriptyline (more sedating drugs) on
symptoms of anxiety or insomnia may beome liabilities over time. 2hese drugs often
ontinue to be sedating in the longer run, ;hih an lead to patients prematurely
disontinuing mediation and inrease the risk of relapse or reurrene. Some
pratitioners use adjuntive mediations (e.g., sleeping pills or anxiolytis) ombined
;ith antidepressants to provide more immediate symptom relief or to over those side
effets to ;hih most patients ultimately adapt.
+ patient<s prior treatment history is important, beause an earlier response typially
predits urrent response. + doumented failure on a properly onduted trial of a
partiular antidepressant lass (e.g., SS0@s, triylis, or ,+>@s) suggests hoosing an
agent from an alternative lass. 2he history of a first#degree relative responding to a
partiular drug is assoiated ;ith a good response to the same lass of agents in the
+ute 2reatment 'ailures
Patients may not respond to a mediation, beause ()) they annot tolerate the side
effets, even in the fae of a good linial responseB (") an idiosynrati adverse event
may ourB (() the linial response is not ade?uateB or (1) the ;rong diagnosis has been
made. +ute phase mediation trials should last 1 to 3 ;eeks to determine if meaningful
symptom redution is attained. ,ost (but not all) patients ;ho ultimately respond fully
sho; at least a partial response (i.e., at least a "/ to "$ perent redution in pretreatment
depressive symptom severity) by ;eek 1 if the dose is ade?uate during the initial ;eeks
of treatment. 7ak of a partial response by 1 to 3 ;eeks indiates that a treatment hange
is needed. 7onger time periodsDEF6 to )" ;eeks or longerDEFare needed to define the
ultimate degree of symptom redution ahievable ;ith a mediation. +pproximately one
half of patients re?uire a seond mediation treatment trial beause the initial treatment is
poorly tolerated or ineffetive.
Seleting Seond 2reatment >ptions
Ahen the initial treatment is unsuessful, s;ithing to an alternative treatment, or
augmenting the urrent treatment is a ommon option. 2he hoie bet;een s;ithing
from the initial single treatment to a ne; single treatment (as opposed to adding a seond
treatment to the first one) rests on the patient<s prior treatment history, the degree of
benefit ahieved ;ith the initial treatment, and patient preferene. +s a rule, s;ithing
rather than augmenting is preferred after an initial mediation failure. >n the other hand,
augmentation strategies are helpful ;ith patients ;ho have gained some benefit from the
initial treatment but ;ho have not ahieved remission. 2he best#doumented
augmentation strategies involve lithium (!skalith) or thyroid hormone. + ombination of
an SS0@ and bupropion (Aellbutrin) is also ;idely employed. @n fat, no ombination
strategy has been onlusively sho;n to be more effetive than another. !42 is effetive
in psyhoti and nonpsyhoti forms of depression, but is reommended generally only
for repeatedly nonresponsive ases or in patients ;ith very severe disorders.
&a"le +#,+$-. US /ood and Drug (dministration (/D()$(pproved )edications for t!e
&reatment of Bipolar Disorders
(gent )ania )aintenance
+ripipra=ole (+bilify) 9es ("//1) Go
4arbama=epine T0 (!?uetro) 9es ("//1) Go
.ivalproex (.epakote) 9es ()883) Go
7amotrigine (7amital) Go 9es ("//()
7ithium (7ithobid) 9es ()85/) 9es ()851)
>lan=apine (Nyprexa) 9es ("///) 9es ("//1)
0isperidone (0isperdal) 9es ("//() Go
Uuetiapine (Sero?uel) 9es ("//1) Go
Niprasidone (Geodon) 9es ("//1) Go
4ombined 2reatment
,ediation and formal psyhotherapy are often ombined in pratie. @f physiians vie;
mood disorders as fundamentally evolving from psyhodynami issues, their
ambivalene about the use of drugs may result in a poor response, nonompliane, and
probably inade?uate dosages for too short a treatment period. +lternatively, if physiians
ignore the psyhosoial needs of a patient, the outome of pharmaotherapy may be
ompromised. Several trials of a ombination of pharmaotherapy and psyhotherapy for
hronially depressed outpatients have sho;n a higher response and higher remission
rates for the ombination than for either treatment used alone.
Bipolar .isorders
2he pharmaologial treatment of bipolar disorders is divided into both aute and
maintenane phases. Bipolar treatment, ho;ever, also involves the formulation of
different strategies for the patient ;ho is experiening mania or hypomania or depression.
2able )$.)#(5 lists CS 'ood and .rug +dministration ('.+)#approved mediations for
the treatment of bipolar disorders. !ah of these mediations is assoiated ;ith a uni?ue
side effet and safety profile, and no one drug is preditably effetive for all patients.
>ften, it is neessary to try several so#alled DEImood stabili=ersDEJ before an optimal
treatment is found.
2reatment of +ute ,ania
2he treatment of aute mania, or hypomania, usually is the easiest phases of bipolar
disorders to treat. +gents an be used alone or in ombination to bring the patient do;n
from a high. Patients ;ith severe mania are best treated in the hospital ;here aggressive
dosing is possible and an ade?uate response an be ahieved ;ithin days or ;eeks.
+dherene to treatment, ho;ever, is often a problem, beause patients ;ith mania
fre?uently lak insight into their illness, and refuse to take mediation. Beause impaired
judgment, impulsivity, and aggressiveness ombine to put the patient or others at risk,
many patients in the mani phase are mediated to protet themselves and others from
7ithium 4arbonate
7ithium arbonate is onsidered the prototypial DEImood stabili=er.DEJ 9et, beause
the onset of antimani ation ;ith lithium an be slo;, it usually is supplemented in the
early phases of treatment by atypial antipsyhotis, mood#stabili=ing antionvulsants, or
high#poteny ben=odia=epines. 2herapeuti lithium levels are bet;een /.3 and )."
m!?O7. 2he aute use of lithium has been limited in reent years by its unpreditable
effiay, problemati side effets, and the need for fre?uent laboratory tests. 2he
introdution of ne;er drugs ;ith more favorable side effets, lo;er toxiity, and less
need for fre?uent laboratory testing has resulted in a deline in lithium use. 'or many
patients, ho;ever, its linial benefits an be remarkable.
Halproate (valproi aid R.epakeneS or divalproex sodium R.epakoteS) has surpassed
lithium in use for aute mania. Cnlike lithium, Halproate is only indiated for aute
mania, although most experts agree it also has prophylati effets. 2ypial dose levels of
valproi aid are 5$/ to ",$// mg per day, ahieving blood levels bet;een $/ and )"/
PVgOm7. 0apid oral loading ;ith )$ to "/ mgOkg of divalproex sodium from day ) of
treatment has been ;ell tolerated and assoiated ;ith a rapid onset of response. + number
of laboratory tests are re?uired during valproate treatment.
4arbama=epine and >xarba=epine
4arbama=epine has been used ;orld;ide for deades as a first#line treatment for aute
mania, but has only gained approval in the Cnited States in "//1. 2ypial doses of
arbama=epine to treat aute mania range bet;een 3// and ),6// mg per day assoiated
;ith blood levels of bet;een 1 and )" PVgOm7. 2he keto ongener of arbama=epine,
oxarba=epine, may possess similar antimani properties. &igher doses than those of
arbama=epine are re?uired, beause ),$// mg of oxarba=epine approximates ),/// mg
of arbama=epine.
4lona=epam and 7ora=epam
2he high#poteny ben=odia=epine antionvulsants used in aute mania inlude
lona=epam (-lonopin) and lora=epam (+tivan). Both may be effetive and are ;idely
used for adjuntive treatment of aute mani agitation, insomnia, aggression, and
dysphoria, as ;ell as pani. 2he safety and the benign side effet profile of these agents
render them ideal adjunts to lithium, arbama=epine, or valproate.
+typial and 2ypial +ntipsyhotis
+ll of the atypial antipsyhotisDEFolan=apine, risperidone, ?uetiapine, =iprasidone, and
aripipra=oleDEFhave demonstrated antimani effiay and are '.+ approved for this
indiation. 4ompared ;ith older agents, suh as haloperidol (&aldol) and hlorproma=ine
(2hora=ine), atypial antipsyhotis have a lesser liability for exitatory postsynapti
potential and tardive dyskinesiaB many do not inrease prolatin. &o;ever, they have a
;ide range of substantial to no risk for ;eight gain ;ith its assoiated problems of insulin
resistane, diabetes, hyperlipidemia, hyperholesteremia, and ardiovasular impairment.
Some patients, ho;ever, re?uire maintenane treatment ;ith an antipsyhoti mediation.
2reatment of +ute Bipolar .epression
2he relative usefulness of standard antidepressants in bipolar illness, in general, and in
rapid yling and mixed states, in partiular, remains ontroversial beause of their
propensity to indue yling, mania, or hypomania. +ordingly, antidepressant drugs are
often enhaned by a mood stabili=er in the first#line treatment for a first or isolated
episode of bipolar depression. + fixed ombination of olan=apine and fluoxetine
(Symbyax) has been sho;n to be effetive in treating aute bipolar depression for an 6#
;eek period ;ithout induing a s;ith to mania or hypomania.
Paradoxially, many patients ;ho are bipolar in the depressed phase do not respond to
treatment ;ith standard antidepressants. @n these instanes, lamotrigine or lo; dose
=iprasidone ("/ to 6/ mg per day) may prove effetive.
!letroonvulsive therapy may also be useful for bipolar depressed patients ;ho do not
respond to lithium or other mood stabili=ers and their adjunts, partiularly in ases in
;hih intense suiidal tendeny presents as a medial emergeny.
>ther +gents
Ahen standard treatments fail, other types of ompounds may prove effetive. 2he
alium hannel antagonist verapamil (4alan, @soptin) has aute antimani effiay.
Gabapentin, topiramate, =onisamide, levetiraetam, and tiagabine have not been sho;n to
have aute antimania effets, although some patients may benefit from a trial of these
agents ;hen standard therapies have failed. 7amotrigine does not possess aute antimani
properties, but does help prevent reurrene of mani episodes. Small studies suggest the
potential aute antimani and prophylati effiay of phenytoin. !42 is effetive in
aute mania. Bilateral treatments are re?uired, as unilateral, nondominant treatments have
been reported to be ineffetive or even to exaerbate mani symptoms. !42 is reserved
for the patient ;ith rare refratory mania or for the patient ;ith medial ompliations, as
;ell as extreme exhaustion (malignant hyperthermia or lethal atatonia).
,aintenane 2reatment of Bipolar .isorder
Preventing reurrenes of mood episodes is the greatest hallenge faing the liniian.
Got only must the hosen regimen ahieve its primary goalDEFsustained euthymiaDEFbut
the mediations should not produe un;anted side effets that affet funtioning.
Sedation, ognitive impairment, tremor, ;eight gain, and rash are some side effets that
lead to treatment disontinuation.
&a"le +#,+$-0 'rinciples in t!e &reatment of Bipolar Disorders
,aintain dual treatment fous* ()) aute short term and (") prophylaxis.
4hart illness retrospetively and prospetively.
,ania as medial emergeny* 2reat first, hemistries later.
7oad valproate and lithium (!skalith)B titrate lamotrigine (7amital) slo;ly.
4areful ombination treatment an derease adverse effets.
+ugment rather than substitute in treatment#resistant patient.
0etain lithium in regimen for its antisuiide and neuroprotetive effets.
2aper lithium slo;ly, if at all.
!duate patient and family about illness and risk#to#benefit ratios of aute and prophylati
Give statistis (i.e., $/ perent relapse in first $ months off lithium).
+ssess ompliane and suiidality regularly.
.evelop an early ;arning system for identifiation and treatment of emergent symptoms.
4ontrat ;ith patient as needed for suiide and substane use avoidane.
Cse regular visitsB monitor ourse and adverse effets.
+rrange for interval phone ontat ;hen needed.
.evelop fire drill for mania reemergene.
@n?uire about and address omorbid alohol and substane abuse.
2argeted psyhotherapyB use mediali=ation of illness.
2reat patient as a oinvestigator in the development of effetive linial approahes to the
@f treatment is suessful, be onservative in making hanges, maintain the ourse, and
ontinue full#dose pharmaoprophylaxis in absene of side effets.
@f treatment response is inade?uate, be aggressive in searhing for more effetive alternatives.
7ithium, arbama=epine, and valproi aid, alone or in ombination, are the most ;idely
used agents in the long#term treatment of patients ;ho are bipolar. 7amotrigine has
prophylati antidepressant and, potentially, mood#stabili=ing properties. Patients on
lamotrigine ;ith bipolar @ disorder depression exhibit a rate of s;ith into mania that is
the same as the rate ;ith plaebo. 7amotrigine appears to have superior aute and
prophylati antidepressant properties ompared ;ith antimani properties. Given that
breakthrough depressions are a diffiult problem during prophylaxis, lamotrigine has a
uni?ue therapeuti role. Hery slo; inreases of lamotrigine help avoid the rare side effet
of lethal rash. + "// mg per day dose appears to be the average in many studies. 2he
inidene of severe rash (i.e., Stevens#:ohnson syndrome, a toxi epidermal nerolysis) is
no; thought to be approximately " in )/,/// adults and 1 in )/,/// hildren.
2hyroid supplementation is fre?uently neessary during long#term treatment. ,any
patients treated ;ith lithium develop hypothyroidism, and many patients ;ith bipolar
disorder have idiopathi thyroid dysfuntion. 2
("$ to $/ PVg per day), beause of its
short half#life, is often reommended for aute augmentation strategies, ;hereas 2
fre?uently used for long#term maintenane. @n some enters, hypermetaboli doses of
hormone are used. .ata indiate improvement in both mani and depressive phases ;ith
hypermetaboli 2
augmenting strategies. 2able )$.)#(6 summari=es the priniples of
treatment of bipolar disorders.
'@GC0! )$.)#3 Statues from the .epression +;areness 0eognition and 2reatment (.O+02)
ampaign. (4ourtesy of the Gational 7ibrary of ,ediine.)
.epression +;areness, 0eognition and 2reatment
2he .epression +;areness, 0eognition and 2reatment program (.O+02) is a
multiphase information and eduation program designed to alert health professionals and
the general publi to the fat that depressive disorders are ommon, serious, and treatable.
@t ;as launhed by the G@,& in )866 to enhane the availability and ?uality of treatment
for depression ('ig. )$.)#3).