BIOLOGICAL TREATMENTBIOLOGICAL TREATMENT

dr. A.A.A.A. Kusumawardhani,SpKJ(K)dr. A.A.A.A. Kusumawardhani,SpKJ(K)

20092009

Psychiatric treatmentPsychiatric treatment Comprehensive – Eclectic-HolisticComprehensive – Eclectic-Holistic

Socio-cultural

Psycho-educative

Organo-biologic

Therapy in PsychiatryTherapy in Psychiatry Biological / Physical treatment:Biological / Physical treatment:

a. Drugs / Psycho-pharmacotherapya. Drugs / Psycho-pharmacotherapyb. ECT/ Electro Convulsion Therapyb. ECT/ Electro Convulsion Therapyc. Othersc. Others

Psychological treatment:Psychological treatment:- Psychotherapy - Psychotherapy individual/groupindividual/group

- Psychotherapy - Psychotherapy - - supportivesupportive- re-educative- re-educative- re-constructive- re-constructive

Psycho-pharmacotherapyPsycho-pharmacotherapy PSYCHOTROPIC DRUGSPSYCHOTROPIC DRUGS

> Major action at CNS :> Major action at CNS :- Thinking process- Thinking process- Mood- Mood

- Motoric function / behaviour- Motoric function / behaviour Clinical effect Clinical effect Clasification: Clasification:

1. Antipsychotics/Neuroleptic/Major Tranquilizer1. Antipsychotics/Neuroleptic/Major Tranquilizer2. Antidepresant2. Antidepresant3. Antianxiety/Anxyolytic sedatives/Minor Tranq.3. Antianxiety/Anxyolytic sedatives/Minor Tranq.4. Antimanic/Mood stabilizer4. Antimanic/Mood stabilizer

AntipsychoticsAntipsychotics Classification:Classification:

* Typical * Typical DA DA phenothiazine &phenothiazine &

NonfenothiazineNonfenothiazine

* Atypical* Atypical SDA SDA

# High Potency# High Potency# Low Potency# Low Potency

Pharmacokinetic of antipsychotics (1)Pharmacokinetic of antipsychotics (1)

Age : geriatric Age : geriatric clearence clearence Genetic : ethnics Genetic : ethnics different metabolism different metabolism Substance Abuse behaviour :Substance Abuse behaviour :

* smoking * smoking metabolismsmetabolisms* alcohol * alcohol metabolisms,metabolisms,

liver function & nutritionliver function & nutrition Medical condition :Medical condition :

* liver diseases, ex. Cirrhosis hepatis* liver diseases, ex. Cirrhosis hepatis* Congestive Heart failure* Congestive Heart failureblood flowblood flow clearenceclearence

Pharmacokinetic of antipsychotics (2)Pharmacokinetic of antipsychotics (2)

Enzyme inducersEnzyme inducers*carbamazepine, phenytoin, *carbamazepine, phenytoin, ethambutol, barbiturateethambutol, barbiturate

Clearance InhibitorsClearance Inhibitors* SSRI, TCA, beta blocker dll.* SSRI, TCA, beta blocker dll.

Changes in binding proteinChanges in binding protein* stress, hipoalbumin, * stress, hipoalbumin, hepatic/renal failure.hepatic/renal failure.

PharmacodynamicPharmacodynamic

Mode of action : DA & SDA Mode of action : DA & SDA psychotics symptoms (hallucination, psychotics symptoms (hallucination,

delusion, etc.)delusion, etc.)

Dopamine Receptor Antagonis:Dopamine Receptor Antagonis:* nigrostriatal system* nigrostriatal system* mesolimbocortical system* mesolimbocortical system* tuberoinfundibuler system* tuberoinfundibuler system

Nigrostriatal pathway Substantia Nigra to Striatum . Motor control . Death of neurons in this pathway can result in Parkinson's Disease

Tuberoinfundibular pathway Hypothalamus to Pituitary gland . Hormonal regulation . Maternal behavior (nurturing) . Pregnancy . Sensory processes

Mesolimbic and Mesocortical pathways Ventral Tegmental Area to Nucleus Accumbens, Amygdala & Hippocampus, and Prefrontal Cortex . Memory . Motivation and emotional response . Reward and desire . Addiction . Can cause hallucinations and

schizophrenia if not functioning properly

Dopamine Pathway

Release of dopamine (green) at synapses from an axon terminal (left). Dopamine is shown binding to receptors on the postsynaptic membrane (right).

Dopamine receptors being blocked by an antipsychotic drug (red). Dopamine can no longer bind to the receptors on the post-synaptic membrane, so it is as if there is less dopamine in the brain.

Classification Classification (chemical structure)(chemical structure)

Phenothiazines Phenothiazines - Aliphatic : Chlorpromazine, - Aliphatic : Chlorpromazine,

Promazine, Promazine, TriflupromazineTriflupromazine- Piperidine : Thioridazine, - Piperidine : Thioridazine,

Promazine, Promazine,- Piperazine : Fluphenazine, - Piperazine : Fluphenazine,

Trifluoperazine Trifluoperazine

Thioxanthenes : Chlorprothixine, Thioxanthenes : Chlorprothixine, ThiothixeneThiothixene

Butyrophenones : Haloperidol, Butyrophenones : Haloperidol, DroperidolDroperidol

Dibenzoxazepine : LoxapineDibenzoxazepine : Loxapine Dihydroindoles : MolindoneDihydroindoles : Molindone Diphenylbutylpiperidines : PimozideDiphenylbutylpiperidines : Pimozide

Classification Classification (chemical structure)(chemical structure)

Side effects (1)Side effects (1) Neurologic :Neurologic :

*acute *acute (acute extrapyramidal syndrome)(acute extrapyramidal syndrome)# acathisia# acathisia# acute dystonia# acute dystonia# parkinsonism# parkinsonism# # Neuroleptic Malignan Syndrome Neuroleptic Malignan Syndrome

*chronic*chronic# tardive dyskinesia# tardive dyskinesia

Side effects (2)Side effects (2)

Cardiovascular effectCardiovascular effect* Orthostatic (Postural) Hypotension* Orthostatic (Postural) Hypotension* Sudden Unexplained Death* Sudden Unexplained Death

GITGIT* peripheral anticholinergic effects* peripheral anticholinergic effects

Liver, hepatology, renal, skin & eyeLiver, hepatology, renal, skin & eye Endocrinal dysfunctionEndocrinal dysfunction Sexual dysfunctionSexual dysfunction

Treatment PrincipalTreatment PrincipalInitialInitial

gradually increase dosage --> gradually increase dosage --> optimal dose ( 1 – 3 weeks)optimal dose ( 1 – 3 weeks)

Stabilisation (up to 8-10 weeks)Stabilisation (up to 8-10 weeks)Maintenance (months – years)Maintenance (months – years)

Side effects management (1)Side effects management (1) SE Parkinsonism SE Parkinsonism use antiparkinsons use antiparkinsons

drugs, such as:drugs, such as:* artane (trihexyphenidil)* artane (trihexyphenidil)* congentin (benztropin)* congentin (benztropin)* diphenhydramin (benadryl)* diphenhydramin (benadryl)(do not use routinely)(do not use routinely)

NMS :NMS :*stop antypsychotic*stop antypsychotic*treat symptomatically*treat symptomatically*observe vital signs*observe vital signs

Side effects management (2)Side effects management (2)

Tardive dyskinesia :Tardive dyskinesia :* make a clear diagnosis * make a clear diagnosis ensure ensure effective APeffective AP* use only minimal dose* use only minimal dose* caution in usage for children, geriatric, * caution in usage for children, geriatric, and patients with mood disorders and patients with mood disorders * do regular examination for side effects* do regular examination for side effects* TD + * TD + give an informed consent, lower give an informed consent, lower the dosage the dosage change drug change drug * when TD getting worse * when TD getting worse stop the drug stop the drug change/try Clozapin change/try Clozapin

ANTIDEPRESANTANTIDEPRESANT Classification. Classification.

* derivative of tricyclic AD* derivative of tricyclic ADImipraminImipramin - Tofranil- TofranilAmitriptilinAmitriptilin- Laroxyl- LaroxylAmineptinAmineptin - Survector- Survector

* derivative of tetracyclic AD* derivative of tetracyclic ADMaproptilinMaproptilin - Ludiomil- LudiomilMianserinMianserin - Tolvon- Tolvon

Antidepresant (1)Antidepresant (1)

•Monoaminoxidase InhibitorMonoaminoxidase InhibitorMAOI & RIMA MAOI & RIMA

-moclobemide (Aurorix)-moclobemide (Aurorix) •Serotonergic (SSRI)Serotonergic (SSRI)

- Sertralin- Sertralin- Fluoxetine- Fluoxetine- Fluvoxamin- Fluvoxamin- Paroxetin- Paroxetin

Antidepresant (2)Antidepresant (2)

Purpose:Purpose:Heal / decrease depresive symptomsHeal / decrease depresive symptoms

Mode of action :Mode of action :Increase NT concentration especially Increase NT concentration especially norepinephrin & serotoninnorepinephrin & serotonin

Antidepresant (3)Antidepresant (3)

Side effects:Side effects: 1. Hypotension (geriatric)1. Hypotension (geriatric)

2. Cardio effects (EKG abnormality)2. Cardio effects (EKG abnormality)3. Otonomic symptoms3. Otonomic symptoms4. CNS effect4. CNS effect5. Allergy5. Allergy6. hematology problems6. hematology problems7. psychological symptoms (manic, 7. psychological symptoms (manic, restlessness)restlessness)

Antidepresant (3)Antidepresant (3)

MAOI side effects:MAOI side effects:

- hypotension & hypertension- hypotension & hypertension- hepatologic problem- hepatologic problem- otonomic- otonomic- neurological (paresthesia,convulsion)- neurological (paresthesia,convulsion)- oedema- oedema- hematologic- hematologic- psychologic disturbances- psychologic disturbances- crisis hypertention - crisis hypertention

Antidepresant (4)Antidepresant (4)

Treatment Principals:Treatment Principals:- start from low dosage - start from low dosage therapeutical effect appears within therapeutical effect appears within 2 / 3 weeks 2 / 3 weeks- maintenance phase minimal 6 - maintenance phase minimal 6 months & can last for 3 – 5 yearsmonths & can last for 3 – 5 years

Tricyclic AntidepressantTricyclic Antidepressant

Selective Serotonin Reuptake InhibitorsSelective Serotonin Reuptake Inhibitors

Monoamine Oxidase InhibitorMonoamine Oxidase Inhibitor

MAOI

ANTIANXIETYANTIANXIETY CLASSIFICATIONCLASSIFICATION

1. Derivative of Benzodiazepine1. Derivative of Benzodiazepine- diazepam- diazepam - valium- valium- bromazepam- bromazepam - lexotan- lexotan- lorazepam- lorazepam - ativan- ativan- clobazam- clobazam - frisium- frisium- alprazolam- alprazolam - xanax- xanax

BuspironBuspiron -buspar-buspar2. Derivative of Gliserol2. Derivative of Gliserol - - meprobamatmeprobamat

3. Der. Of Barbiturate - ph3. Der. Of Barbiturate - phenobarbitalenobarbital

Antianxiety (1)Antianxiety (1)

Purpose :Purpose :Decrease anxietyDecrease anxiety- sedative effects- sedative effects- relaxation- relaxation- amnesia- amnesia- antiepilepsy- antiepilepsy

Therapeutic Principal:Therapeutic Principal:- do not use high dosage - do not use high dosage - do not use more than 1 month- do not use more than 1 month

Antianxiety (2)Antianxiety (2)

Side EffectsSide Effects- drowsiness- drowsiness- headache- headache- dysarthri- dysarthri- ataxia- ataxia- appetite - appetite - dependent- dependent- withdrawal effects- withdrawal effects

MOOD STABILIZERMOOD STABILIZER

Main purpose: control manic Main purpose: control manic condition & prevent relapsescondition & prevent relapses

Lithium :Lithium :Indications: manic/depressive Indications: manic/depressive episodeepisodeEffective doses : Effective doses : 0.8 – 1.5 mEq/l plasma level 0.8 – 1.5 mEq/l plasma level (start with 300 mg/day p.o)(start with 300 mg/day p.o)

Antimanic (1)Antimanic (1)

Side Effecs :Side Effecs :- soft tremor - soft tremor - diarrhea & vomiting- diarrhea & vomiting- fatigue & vertigo- fatigue & vertigo- ataxia & rough tremor - ataxia & rough tremor - declining consciousness- declining consciousness- convulsion- convulsion- oligouria & anuria- oligouria & anuria- oedeme- oedeme

Antimanic (2)Antimanic (2)

““Mood Stabilizer”Mood Stabilizer”

1. Lithium salt1. Lithium salt

Lithium carbonateLithium carbonate - Priadel- Priadel

- Theralith- Theralith

2. Others2. Others

CarbamazepineCarbamazepine - Tegretol- Tegretol

Valproic Acid/DevalproateValproic Acid/Devalproate - Depakote- Depakote

ELECTRO CONVULSION ELECTRO CONVULSION THERAPY (ECT)THERAPY (ECT)

Main Indication: Major DepressionMain Indication: Major Depression

Electrify the brain (using 2 Electrify the brain (using 2 elektrodes placed on temporal elektrodes placed on temporal region)region) convulsion like that of grandmal convulsion like that of grandmal epilepticepileptic

ECT (1)ECT (1)

Preparation :Preparation :- patient physical check up - patient physical check up (Cardiovascular,pulmo,bones,brain)(Cardiovascular,pulmo,bones,brain)- Informed consent- Informed consent- fasting minimal 6 hours before ECT- fasting minimal 6 hours before ECT- prepare the patient to remain calm : - prepare the patient to remain calm : distract their attention, give distract their attention, give premedicationpremedication- remove false teeth, jewelry, hair pin- remove false teeth, jewelry, hair pin- nurse assistance for preventing- nurse assistance for preventingluxasio/fractureluxasio/fracture

ECT (2)ECT (2)

Tools preparation :Tools preparation :- ECT machine- ECT machine- wet cotton for underlying - wet cotton for underlying electrodeselectrodes- oxygen tube & mask- oxygen tube & mask- mucous suction- mucous suction- drugs : coramine, adrenalin - drugs : coramine, adrenalin - rubber teeth holder- rubber teeth holder- flat bed - flat bed

ECT (3)ECT (3)

Execution :Execution :- Patient is laid down without pillow, in - Patient is laid down without pillow, in baggy hospital clothesbaggy hospital clothes- Rubber teeth holder- Rubber teeth holder Nurses hold : lower jaw/ head; Nurses hold : lower jaw/ head; shoulder; hip & kneeshoulder; hip & knee- Doctor place the elektrodes- Doctor place the elektrodes tonic tonic convulsion -->clonic convulsionconvulsion -->clonic convulsion apneuapneubreath normally breath normally (important (important phase)phase)

ECT (4)ECT (4)

Post ECT observation :Post ECT observation :- important - important - until vital condition become normal, - until vital condition become normal, still unconcious, usually falling still unconcious, usually falling asleep; sometimes restless & moving asleep; sometimes restless & moving uncontrollablyuncontrollably nurses must keep watching until nurses must keep watching until the patient is fully councious.the patient is fully councious.

ECT (5)ECT (5)

- after regaining consciousness, the - after regaining consciousness, the patient often confused, disoriented patient often confused, disoriented and amnesticand amnestic nurses help orientation and nurses help orientation and memory by communicating in memory by communicating in stages, giving a calming and non-stages, giving a calming and non-irritating environment.irritating environment.

OTHER BIOLOGICAL OTHER BIOLOGICAL THERAPYTHERAPY

Light therapyLight therapy Sleep Deprivation & Alteration of Sleep Deprivation & Alteration of

Sleep SchedulesSleep Schedules PsychosurgeryPsychosurgery Orthomolecular therapyOrthomolecular therapy Subcoma Insulin therapySubcoma Insulin therapy Coma therapyComa therapy Carbon Dioxide therapyCarbon Dioxide therapy

Resource:Resource: Comprehensive Texbook of Comprehensive Texbook of

Psychiatry –Kaplan HI, Saddock BJPsychiatry –Kaplan HI, Saddock BJ