Tugas 2. PRESENTASI PSIKOSOMATIK 3 (2).pptx

1
(Benzodiazepine, Antidepressan
trisiklik, SSRI, SNRI)
PSIKOFARMAKA

09/08/2025 2
 Psikofarmaka dan psikoterapi pada
gangguan psikosomatik akan
memperbaiki gejala klinis
 Psikofarmaka pada gangguan
psikosomatik bekerja dengan
mempengaruhi perasaan (afek) dan
emosi serta fungsi vegetatif yang
berkaitan
 Organ sasaran yang dirasa sakit dan
yang harus diobati biasanya hanya
dipengaruhi secara tidak langsung
 Efek psikofarmaka pada kelainan
organik akan berkurang disebabkan
karena peningkatan atau
memburuknya penyakit fisik
 Pada gangguan psikosomatik yang
bersamaan dengan kelainan organik
proses organik akan memengaruhi
atau mengurangi khasiat
psikofarmaka.
PENDAHULUAN
Mudjaddid E, Budihalim S, Sukatman D. Psikofarmaka dan Psikosomatik dalam Buku Ajar Ilmu Penyakit Dalam Edisi VII.
2023:4374-6

09/08/2025 3
 Pemberian psikoterapi dan
psikofarmaka secara serentak
diperlukan untuk mendapat hasil lebih
baik
 Tanpa psikoterapi pasien tidak
mendapatkan "dukungan" sehingga
tidak mampu mengatasi persoalan dan
beban hidupnya
 Dikenal beberapa golongan senyawa
psikofarmaka antara lain:
 Obat tidur (sedatif dan hipnotik)
 Obat penenang minor
 Obat penenang mayor (neuroleptik)
 Antidepresan
PENDAHULUAN
2023:4374-6

09/08/2025 4
 Diberikan jangka waktu pendek, 2-4 minggu
 Dianjurkan golongan benzodiazepin seperti: nitrozepam, flurazepam, triazolam
 Obat sedatif golongan non benzodiazepin yang dipakai saat ini Zolpidem
 Pada insomnia dengan kegelisahan (ansietas), senyawa fenotiazin: Tioridazin,
Prometazin.
OBAT TIDUR (SEDATIF DAN HIPNOTIK)
2023:4374-6

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 Diazepam paling efektif pada ansietas, agitasi, spasme otot, delirium tremens,
hingga epilepsi
 Benzodiazepin hanya diberikan pada ansietas hebat, maksimal 2 bulan, kemudian
tapering off
 Golongan benzodiazepin lain seperti klobazam dan lorazepam dapat dipakai sebagai
anti ansietas
OBAT PENENANG MINOR (MINOR TRANQUILLIZER)
2023:4374-6

09/08/2025 6
 A class of psychoactive drugs known
for their depressant effect on CNS
 Primarily work on the GABA-A receptor
subunit neurotransmitter
 Quickly diffuse through the blood–
brain barrier to affect the inhibitory
neurotransmitter GABA and exert
sedative effects
 Most important subunit of GABA-A
receptor is the alpha (A) submit unit.
 The alpha subunit has various
isoforms, which dictate a BZD’s effects
on the CNS
 The A1 subunit responsible for the
sedative effects and anterograde
amnesia, and some of the
anticonvulsive impacts of diazepam
 The A2 subunit isoform mediates the
anxiolytic and myorelaxant effects
BENZODIAZEPINE
Edinoff AN, Nix CA, Hollier J, Sagrera CE, Delacroix BM, Abubakar T, et al. Benzodiazepines: Uses, Dangers, and Clinical Considerations. Neurol Int. 2021. Nov
10;13(4):594-607

09/08/2025 7
 Four clinical properties:
 Sedative
 Anxiolytic
 skeletal muscle relaxant
 Antiepileptic
 Have rapid onset and immediate
symptom relief
 Metabolized primarily by the liver and
excreted by conjugation
 Should be used in caution in the
elderly, smokers, and those with liver
disease or damage
 In elderly, the medication can lower
the seizure threshold, cause gait
instability, and balance problems
BENZODIAZEPINE
10;13(4):594-607

09/08/2025 8
 The sedative effect aids in sleep and
insomnia disorders by reducing sleep
onset latency
 The CNS depressant effects reduce
anxiety and abort acute-onset panic
and anxiety attacks
 Incredibly effective at rapidly aborting
convulsant activity in epilepsy/other
seizure disorders
 Discontinuation after chronic use
leads to withdrawal symptoms
BENZODIAZEPINE: INDICATION
Edinoff AN, Nix CA, Hollier J, Sagrera CE, Delacroix BM, Abubakar T, et al. Benzodiazepines: Uses, Dangers, and Clinical Considerations. Neurol Int. 2021.
Nov 10;13(4):594-607

09/08/2025 9
 Due to its short half-life, and rapid
absorption, alprazolam is
distinguished as one of the most
rapid-acting BZD with fastest relief of
symptomology
 Widely used as monotherapy for panic
disorder and anxiety
 Found superior to other forms of
monotherapy for these conditions
including other BZD, non-SSRI
antidepressants, and buspirone
 This superior effect is to be due to its
unique alpha-2 adrenergic activity,
enhancing its potency for relieving
panic and anxiety disorders
 This same mechanism is also thought
to be the cause behind alprazolam’s
strong rebound hyperadrenergic
effects with cessation
BENZODIAZEPINE : ALPRAZOLAM
Nov 10;13(4):594-607

09/08/2025 10
Jameson JL, Faiuci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Psychiatric Medications in Harrison’s manual of medicine. 2020: 1105-10

09/08/2025 11
 The risk of falls leading to injuries in
elderly BZD users is significantly
increased in patients greater than 80
years old
 For mothers with BZD use during
pregnancy, there is a risk of premature
birth and low birth weight
 One of the debilitating side effects is
their addictive potential
 The dependence on BZDs generally
leads to withdrawal symptoms, which
necessitates careful tapering of the
medication when prescribed
BENZODIAZEPINE : ADVERSE EFFECT
10;13(4):594-607

09/08/2025 12
 Regular use of BZDs cause serious,
harmful psychological and physical
dependence
 Regular use lead to tolerance 
physiologic dependence on the
presence of BZDs in the body’s system
 Symptoms associated with withdrawal
occur due to the chronic effect on the
GABA-A receptors in the CNS to BZDs
 Causes a neuroadaptive process of
both desensitization of the inhibitory
function of GABA, sensitization of
excitatory glutamine receptors, and
possibly sensitization of N-methyl-D-
aspartate (NMDA) receptors, along
with other receptors
 The BZD concentration in blood and
tissue declines causing symptoms
opposite to therapeutic effects.
 These symptoms may last for one to a
few weeks after cessation
BENZODIAZEPINE : WITHDRAWAL SYNDROME
Nov 10;13(4):594-607

09/08/2025 13
 Current treatment of choice is
to switch the current short-
acting BZD for a long-acting
alternative then gradually
taper the dose to wean the
individual off BZD completely
 A gradual taper with
clonazepam is used as
maintenance therapy
 It still carries the risk for
abuse and dependence since
this is also a BZD, albeit a
slow-acting one
BENZODIAZEPINE : WITHDRAWAL SYNDROME
Psychological symptom Physical symptom
• Increased excitability
• Nightmares
• Anxiety
• Insomnia
• Panic attacks
• Depression
• Hallucinations
• Irritability
• Paranoid thoughts
• Social phobia
• Poor memory
• Poor concentration
• Delirium
• Psychosis
• Headache
• Seizures
• Pain or stiffness in the head
and neck region
• Altered sensation of limbs
• Weakness and fatigue
• Tingling and numbness
• Muscle twitches
• Tremors
• Gastrointestinal symptoms
(abdominal distension,
nausea, diarrhea,
constipation, etc.)
• Appetite and weight
changes
• Unusual smell
Nov 10;13(4):594-607

09/08/2025 16
 Jarang diberikan pada pasien gangguan psikosomatik kecuali terdapat
gejala agitasi, gelisah berlebihan, agresi, dan kegaduhan
 Paling sering digunakan senyawa fenotiazin dan butirofenon:
klorpromazin, tioridazin, haloperidol
OBAT PENENANG MAYOR (MAJOR TRANQUILLIZER,
NEUROLEPTICS)
2023:4374-6

09/08/2025 17
 Gejala psikosomatik sering bermanifestasi sebagai depresi, dan depresi sering
merupakan komplikasi penyakit fisis.
 Obat anti depresan yang klasik ialah golongan trisiklik dan tetrasiklik seperti:
amitriptilin, imipramin, mianserin, maprotilin.
 Harus dimulai dengan dosis kecil yang kemudian ditingkatkan
 Diharapkan ada reaksi dalam waktu 2 minggu
 Bila pasien mulai sembuh, pengobatan diteruskan selama 3 bulan dan berangsur-
angsur dosis dapat dikurangi
ANTIDEPRESSANT
2023:4374-6

09/08/2025 18
 Class of medications that were initially
introduced as a pharmacotherapy MDD
 Now regarded as second-line
treatment options alongside SSRI
 The name "tricyclic" due to the
presence of 3 rings in their chemical
structure
 Affect noradrenergic and, to a lesser
extent, serotonergic
neurotransmission but also have
anticholinergic and antihistaminic
effects.
 Inhibiting the reuptake of
neurotransmitters (serotonin,
norepinephrine) modulate mood,
attention, and pain in individuals.
TCAS
Moraczewski J, Awosika AO, Aedma KK. Tricyclic Antidepressants. National Library of Medicine. 2023

09/08/2025 19
 Modulating around 5 distinct
neurotransmitter pathways
 The chemical structure comprises a 3-
ringed arrangement with an attached
secondary or tertiary amine
 Tertiary amines
exhibit significant serotonin reuptake
inhibition, whereas secondary amines
heightened inhibition of
norepinephrine uptake
 Inhibiting serotonin and
norepinephrine reuptake within the
presynaptic terminals  elevated
concentrations within the synaptic
cleft  antidepressant effect
 The neurotransmitters act as
competitive antagonists on
postsynaptic cholinergic (alpha-1 and
alpha-2), muscarinic, and histamine
receptors (H1)
TCAS : MECHANISMS

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 FDA approval for the treatment of
MDD and OCD in individuals aged 10
and older
 The off-label indications:
 Migraine prophylaxis
 Insomnia
 Anxiety
 Chronic pain
 Neuropathic pain such as myofascial pain
 Diabetic neuropathy
 Postherpetic neuralgia
 Demonstrate equivocal efficacy with
SSRIs in MDD, but cause more
significant adverse effects and lower
threshold for overdose
 Utilized as second-line treatment
options for fibromyalgia
 Can be used to treat nocturnal
enuresis in children when
desmopressin ineffective
TCAS : INDICATION

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 Inhibit cholinergic receptors: blurred
vision, constipation, xerostomia,
confusion, urinary retention, and
tachycardia
 The alpha-1 adrenergic receptor
blockade: orthostatic hypotension and
dizziness
 Histamine blockade (H1): sedation,
increased appetite, weight gain
 Induce cardiovascular complications:
arrhythmias such as QTc prolongation,
ventricular fibrillation, and sudden
cardiac death, particularly in
individuals with preexisting ischemic
heart disease
 Elevate the risk of seizures in
individuals with epilepsy
 May cause a minor elevation of liver
enzymes; acute hepatitis is seldom
 Heighten the risk of suicidal ideation
and behavior
TCAS : ADVERSE EFFECTS

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 Should not be prescribed to
individuals with a family history of QTc
interval prolongation or sudden
cardiac death
 Hypersensitivity reactions to a TCA
drug
 Should not be administered
concurrently with MAOIs due to the
risk of developing serotonin syndrome
 Caution in individuals with angle-
closure glaucoma
 Used cautiously in patients with a
history of seizures, might lower the
seizure threshold
TCAS : CONTRAINDICATIONS

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 Exhibit a narrow therapeutic index
 Monitoring for signs of toxicity, such
as QRS-widening on ECG, tremors,
confusion, muscle rigidity, and coma
 All patients should undergo screening
for preexisting cardiac conditions:
prolonged QTc intervals, heart disease,
and a family history of arrhythmias
 Patients with low potassium blood
concentrations should undergo
periodic monitoring
 Obtaining an ECG is recommended in
patients aged 50 and older.
 All patients initiating/currently using
TCAs as medications should be
monitored for the aggravation of
depressive symptoms or new-onset
suicidal thoughts or behaviors
TCAS : MONITORING

09/08/2025 24
 Prone to induce toxicity in the event of
accidental or intentional overdose
 Signs and symptoms: ECG
abnormalities (QTc prolongation and
widened QRS complex), hypotension,
seizures, tremors, coma, xerostomia,
urinary retention, and respiratory
depression
 Management of overdose necessitates
stabilizing the patient and addressing
their acute complications
 Activated charcoal to prevent drug
absorption (must occur within 2 hours
of TCA ingestion)
 Sodium bicarbonate in prolonged QRS
interval to elevate their serum pH
levels and diminish the concentration
of active free TCA
 Lidocaine considered as potential
reversal agent in TCA-induced
cardiotoxicity resistant to sodium
bicarbonate
 TCA-induced seizures should be
provided with benzodiazepines
 Hypotension should receive IV
crystalloids and trial of norepinephrine
if unresponsive
 Signs of respiratory compromise should
be administered respiratory support.
TCAS : TOXICITY

09/08/2025 25
 Predominant effects on serotonergic
neurotransmission
 Inhibiting the reuptake of serotonin
increasing serotonin activity
→
 SSRIs inhibit the serotonin transporter
(SERT) at the presynaptic axon
terminal increased amount of
→
serotonin remains in the synaptic cleft
stimulate postsynaptic receptors for
→
a more extended period
 SSRIs have little effect on other
neurotransmitters, such as dopamine
or norepinephrine
 Have relatively fewer side effects than
TCAs and MAOIs due to fewer effects
on adrenergic, cholinergic, and
histaminergic receptors.
SSRI
Chu A, Wadhwa R. Selective serotonins reuptake inhibitors. National Library of Medicine. 2023

09/08/2025 26
 FDA labeled indications to treat the
following conditions:
 Major depressive disorder
 Generalized anxiety disorder
 Bulimia nervosa
 Bipolar depression
 Obsessive-compulsive disorder
 Panic disorder
 Premenstrual dysphoric disorder
 Treatment-resistant depression
 Post-traumatic stress disorder
 Social anxiety disorder
 Other off-label uses include but are
not limited to:
 Binge eating disorder
 Body dysmorphic disorder
 Fibromyalgia
 premature ejaculation
 Paraphilias
 Autism
 Raynaud phenomenon
 Vasomotor symptoms associated with
menopause
SSRI: INDICATIONS

09/08/2025 27
Contraindication
 Contraindicated with the concurrent
use of MAOIs, linezolid, and other
medications that increase serotonin
levels
 Paroxetine is contraindicated in
pregnancy due to its teratogenic
effects in causing cardiovascular
defects in the first trimester
Monitoring
 The effect of SSRIs may take up to 6 weeks
before the patients feel the effects of
treatment
 All patients < 25 years old should be
continually assessed for suicidal ideation
and other unusual behaviors
 For patients with cardiac risk factors, ECG
to monitor for QT prolongation and
arrhythmias
 Weight and vital sign should be regularly
measured to monitor for adverse changes.
 Anxiety, insomnia, and sexual dysfunction
(delayed ejaculation, decreased sexual
desire, and anorgasmia) require regular
assessment.
SSRI: CONTRAINDICATIONS AND MONITORING

09/08/2025 28
 Possibly increased risk of suicidality
among pediatric and young adult (up
to age 25) populations
 Common side effects: sexual
dysfunction, sleep disturbances,
weight changes, anxiety, dizziness,
xerostomia, headache, and
gastrointestinal distress
 Potential to prolong the QT interval,
fatal arrhythmia, torsade de pointes
 Citalopram has correlations with a
longer QT duration than the other
medications in this class.
 Coagulopathy also correlates with SSRI
use
 Be aware of the risk of serotonin
syndrome in all medications that
increase serotonin activity
 SSRIs are metabolized by and have
effects on the cytochrome P450 system
SSRI: ADVERSE EFFECTS

09/08/2025 29
 Overdose is relatively infrequent due
to their increased safety profile and
tolerability compared to other classes
of antidepressants
 Citalopram and escitalopram have an
increased risk of cardiotoxicity due to
QT prolongation, which can progress
to serious arrhythmias such as
Torsades
 Serotonin syndrome is a life-
threatening consequence of increased
serotonergic activity.
 Serotonin syndrome is characterized
by mental status changes, autonomic
dysfunction, and dystonias.
 Findings may include agitation,
tachycardia, hypertension,
hyperthermia, hyperreflexia, tremor,
nausea, vomiting, and clonus
 There is no definitive treatment for
serotonin syndrome aside from
discontinuing the offending agent,
supportive measures, and
benzodiazepines for agitation
SSRI: TOXICITY

09/08/2025 30
 Potentially life-threatening but
preventable adverse reaction that
may result from the therapeutic
use of antidepressants
 Interaction between two or more
serotonin enhancing drugs or
following an overdose of
antidepressants
 Treatment involves the immediate
removal of the offending agent
and administration of supportive
therapy
 Onset of symptoms is usually
rapid, with 60% patients
presenting within six hours of the
initial precipitating factor
SSRI: SEROTONIN SYNDROME
Bleakley S. Review of the choice and use of antidepressant drugs. CMHP. 2013:18-26

09/08/2025 31
 Pharmacological class of
antidepressant medications that exert
their therapeutic effects by impeding
the reuptake process of both serotonin
and norepinephrine neurotransmitters
 Frequently characterized as dual-
action agents
 The degree to which serotonin and
norepinephrine reuptake is inhibited
depends on the dosage
 Venlafaxine primarily acts as a SSRI
when given a daily dose of 75 mg, but
at higher dosages at 225 mg/day and
375 mg/day significantly affects the
norepinephrine transporter
 Venlafaxine, desvenlafaxine,
duloxetine, mirtazapine, vilazodone,
vortioxetine, and levomilnacipran have
mixed noradrenergic and serotonergic
effects.
SNRI

09/08/2025 32
 The main use of SNRIs is in the
treatment of major depression
 Other indication include treatment of
pain disorders (including neuropathies
and fibromyalgia), generalized anxiety,
vasomotor symptoms of menopause
and stress urinary incontinence
 Most common side effect include
nausea and vomiting, dizziness, and
sweating
 Duloxetine and venlafaxine, in
particular, may cause sexual
dysfunction
 Other side effects include fatigue,
insomnia, and headache
SNRI: INDICATIONS AND ADVERSE EFFECT

09/08/2025 33
 The choice should reflect the patient’s
preference, past experiences, previous
response and any concurrent medical
comorbidity or drug therapy
 In the absence of special features, the
SSRIs are recommended first line
 Fluoxetine has the longest half-life and is
associated with a lower risk of
discontinuation symptoms
 If a patient does not respond within 3-4
weeks to the initial SSRI, check
compliance, then gradually increase the
dose
 If patient fail to respond or cannot
tolerate the first SSRI then switching to
an alternative SSRI or another
antidepressant (such as mirtazapine or a
TCA) is recommended
 Venlafaxine (although less well tolerated)
is a useful option for those who have
CHOOSING ANTIDEPRESSANT
Bleakley S. Review of the choice and use of antidepressant drugs. CMHP. 2013:18-26

09/08/2025 35
 The treatment of depression is often
described in three phases
 Acute phase ( 6-12 weeks) to induce
remission and recovery of function.
 Continuation phase (4-9 months) to reduce
relapse
 Maintenance phase to prevent recurrence
after one year of treatment
 Whenever antidepressants are
discontinued, there is an increased
risk of relapse or recurrence
 Canadian guidelines recommend at
least 6 months of treatment and 2
years or more for those at higher risk
of relapse
 Each episode of depression adds to a
patient’s risk of future episodes, so
indefinite maintenance treatment is
often recommended for patients with
3 or more episodes of depression
ANTIDEPRESSAN : DURATION
Kovich H, Kim W, Quaste AM. Pharmacologic treatment of depression. Am Fam Physician. 2023;107:173-81

09/08/2025 36

09/08/2025 37
 Discontinuation syndrome is a set of
symptoms that can occur after an
abrupt cessation (or marked reduction
in dose) of an antidepressant that was
taken continuously for at least one
month
 Effects typically manifest within two to
four days and can last for several
months
 Typical symptoms: Flulike symptoms,
Insomnia, Nausea, Imbalance, Sensory
disturbances, Hyperarousal
 The symptoms of discontinuation can
be difficult to distinguish from relapse
and recurrence.
 Research shows that a slow medication
taper of at least 14 days is best
practice; a taper of several months
may be needed
 A dose taper of approximately 25%
every four weeks and a faster taper of
12.5% every two weeks are both
reasonable strategies.
 A gradual taper has been shown to
result in as few as 5% of patients
experiencing discontinuation
symptoms
 Use of CBT during the medication
taper may help prevent relapse or
recurrence
ANTIDEPRESSANT : DISCONTINUATION

09/08/2025 38

09/08/2025 39
 For medical disorders affecting
liver and/or renal function, dose
adjustments are often required
with some agents being
contraindicated in hepatic and
renal impairment
 Most antidepressants have not
been extensively tested in hepatic
or renal impairment
 The general approach of ‘start
low and go slow’ is advisable to
minimize the risk of toxic effects.
 in cardiac patients with
arrhythmias and a prolonged QT
interval, citalopram, lithium, TCA
and antipsychotics should be
avoided if possible
 Antidepressants transfer into
breast milk in low concentrations.
 This transfer is thought to be
lower for paroxetine and sertraline
than other antidepressants
 Older adults are at greater risk of
adverse drug reactions, initiating
treatment at one-half of the usual
adult starting dose is often
recommended
 Guidelines recommend sertraline,
duloxetine, or escitalopram as
good first-line options for older
patients
ANTIDEPRESSANT IN MEDICAL CONDITION
Rosenblat JD, Kurdyak P, Cosci F, Berk M, Maes M, Brunoni AR, et al. Depression in the medically ill. ANZJP. 2020; 54:346-66

09/08/2025 40
Rosenblat JD, Kurdyak P, Cosci F, Berk M, Maes M, Brunoni AR, et al. Depression in the medically ill. ANZJP. 2020; 54:346-66

09/08/2025 41
Jameson JL, Faiuci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Psychiatric Medications in Harrison’s manual of medicine. 2020: 1105-10

09/08/2025 43
Obat Mekanisme kerja Efek pada
Kecemasan
Efek pada Depresi Onset efek Efek samping
Benzodiazepin
e
Meningkatkan efek
GABA (neutransmitter
inhibitor)
Efek cepat,
menenangkan,
tetapi berisiko
ketergantungan
Tidak utama untuk
depresi
Kerja cepat
(tergantung
jenisnya,
sekitar 10-
60menit)
Depresi pernapasan,
paradoksikal, overdosis
fatal, Sedasi, gangguan
memori,
ketergantungan
SSRI Menghambat reuptake
serotonin
Sangat efektif
untuk gangguan
kecemasan umum,
sosial, dan panik
Efektif untuk
depresi ringan-
sedang
2-6 minggu Sindrom serotonin,
withdrawal syndrome,
SIADH, Mual, insomnia,
sakit kepala, disfungsi
seksual
SNRI Menghambat reuptake
serotonin dan
norepinefrin
Efektif untuk
kecemasan & nyeri
neuropatik
Efektif untuk
depresi sedang-
berat
2-6 minggu Sindrom serotonin,
withdrawal syndrome,
krisis hipertensi,
Hipertensi, takikardia,
insomnia, mulut kering
TCA Menghambat reuptake
serotonin, norepinefrin,
Dopamin, histamine,
Asetilkolin
Bisa mengurangi
kecemasan tetapi
memiliki lebih
banyak efek
samping
Sangat efektif,
terutama untuk
depresi berat
2-4 minggu Aritmia, overdosis fatal,
delirium, Mulut kering
(efek antikolinergik)
sedasi berat, hipotensi
ortostatik
American Psychiatric Association. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients with Major Depressive Disorder.
NICE Guidelines. (2023). Management of Depression and Anxiety Disorders.

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