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Psychopharmacology

Dr. Adel Alzayed


Kuwait University – Medical College
Department of Psychiatry
Objectives

• Classification of psychotropic medications.


• Indecation of use of psychotropic medications.



• Choose a psychotropic medication rationally.

• Know common & dangerous adverse effects.

• Manage failure of response to a therapeutic trial.


Summary of Medications Role in Psychiatry

• They are part of a comprehensive treatment plan.



• Basic knowledge of medications is important in
daily clinical practice.

• Their prescription by the psychiatrist follows a
systematic approach


Why Medications ?

 Dopaminergic theory of Schizophrenia


 Monoaminergic theory of Mood Disorders


Main Psychopharmacological Drugs

• Antipsychotics
• Antidepresants
• Anxiolytics
• Hypnotics
• Cognitives
• Psychostimulants
Psychopharmacologic Drugs
Work over A Spectrum


Antipsychotics
Antipsychotics
 Treat psychotic symptoms.
Divided into first (typical) and second (atypical)

agents.
Typical/1st generation = D2 receptor antagonist

 Effective against +ve > -ve


 Atypicals/2nd generation = Serotonin-dopamine


antagonists
 Effective against both +ve & -ve sx

 Requires ~ one month for significant antipsychotic


effect
CLASSIFICATION OF ANTIPSYCHOTIC DRUGS

 1. TYPICAL ANTI-PSYCHOTICS
 A. Phenothiazine Derivatives
• Aliphatic Derivative: CHLORPROMAZINE
• Piperidine Derivative: THIORIDAZINE
• Piperazine Derivative: FLUPHENAZINE,
PERPHENAZINE, TRIFLUOPERAZINE

 B. Thioxanthene Derivative: THIOTHIXENE


 C. Butyrophenone: HALOPERIDOL
CLASSIFICATION OF ANTI-PSYCHOTIC DRUGS

2. ATYPICAL ANTI-PSYCHOTICS

• CLOZAPINE
• RISPERIDONE
• SERTINDOLE
• ZIPRASIDONE
• OLANZAPINE
• QUETIAPINE
Typical Antipsychotics
D2 Receptors
Other Receptors
Side Effects of Antipsychotics
 

 High-Potency  Low-Potency

 Extrapyramidal
 Seizures
Symptoms  Sedation
 Tardive Dyskinesia  Orthostatic
 Hyperprolactinemia Hypotension
 Neuroleptic
 Agranulocytosis*
 Anticholinergic side
Malignant
Syndrome (NMS)* effects

 Weight gain


General principles about adverse effects

• Psychopharmacological agents affect the whole


body.

• Remember the common and dangerous side
effects.

• They indicate the drug is working.
Antipsychotics
of the 2nd Generation
 Efficacy

1. Positive symptoms are influenced significantly better than


placebo, and equally or more than by the classical
antidopaminergic neuroleptics.
2. Negative symptoms are reduced significantly better than by
placebo or classical antidopaminergic neuroleptics.
3. Affective symptoms are influenced better than by placebo or
classical antidopaminergic neuroleptics.
4. They significantly reduce or prevent the cognitive
impairment. The reduction is higher in comparison to
classical antidopaminergic neuroleptics.
5. The treatment resistant patients with schizophrenia are
improved significantly better than by placebo and at least
equally as by clozapine.
Antipsychotics
Average Daily Doses in mg

 Typicals
 Atypicals



 Risperidone (4-8)
 Haloperidol (5-15)  Olanzapine (10-

20)

Thioridazine(100-  Quetiapine (600-


300)
1200)
 Chlorpormazine (50-  Clozapine (100-
400)
Lower numbers indicate higher potency 600)
SIDE EFFECTTS OF NEUROLEPTIC DRUGS

A. NEUROLOGIC EFFECTS


 1. ACUTE DYSTONIA : spasm of
muscles tongue, face, neck, back,
may mimic seizures
• During the first 1 -5 days of Rx
• Mechanism unknown
• Rx: anti-parkinson’s agents
 2. AKATHISIA : motor
restlessness
• 5 -60 days
• Mechanism unknown
3. PARKINSONISM
§ bradykinesia, rigidity, tremor, mask
facies,
 shuffling gait seen in 5-30 days
§ Mechanism: antagonism of dopamine
 Rx: anti-parkinson’s agents
4. NEUROLEPTIC MALIGNANT

SYNDROME
§ catatonia, stupor, fever, unstable BP,
 myoglobulinemia after weeks of
treatment
§ Mechanism: antagonism of dopamine
Neuroleptic Malignant Syndrome

• Triad:
– Extreme muscular rigidity.
– High fever.
– Fluctuating blood pressure.
• Investigation:
– CPK
• Treatment:
– ICU
– Promocriptine
 5. PERIODIC TREMOR RABBIT
SYNDROME
Ø Peri-oral tremors after months or years of
treatment
Ø Mechanism : unknown
Ø Rx: Anti-parkinson’s Drugs
6. TARDIVE DYSKINESIA

 Supersensivity of D receptors
(cholinergic def)
Ø oral-facial dyskinesia, choreoathetosis,
dystonia
Ø After months or years of RX
Ø Worse on withdrawal
ADVERSE EFFECTS
 B. BEHAVIORAL EFFECTS
qPseudo-depression; toxic confusional state

C. AUTONOMIC NERVOUS SYSTEM


EFFECTS
qurinary retention, dry mouth, loss of
accomodation, constipation
 (MUSCARINIC CHOLINERGIC BLOCKADE)
qorthostatic hypotension, impotence, failure
ejaculate
 D. METABOLIC & ENDOCRINE
EFFECTS
Ø Weight gain, hyperglycemia,
hyperprolactinemia, amenorrhea-
galactorrhea syndrome, infertility,
impotence in males
 E. TOXIC OR ALLERGIC REACTIONS
Ø Agranulocytosis (clozapine) , cholestatic
jaundice,
 skin eruptions
 F. CARDIAC TOXICITY
Ø Ventricular arrythmias (thioridazine)
G. OCULAR COMPLICATIONS:

Ø “ browning of vision”
CLINICAL INDICATIONS

A. PSYCHIATRY INDICATIONS

• SCHIZOPHRENIA
• SCHIZO-AFFECTIVE DISORDERS
• MANIC EPISODES IN BIPOLAR DISORDERS
• GILLES DE LA TOURETTE SYNDROME
• SENILE DEMENTIA
B. NON-PSYCHIATRIC INDICATION

• ANTI-EMETIC EFFECT
• ANTI-PRURITIC EFFECT
• PRE-OPERATIVE ANESTHESIA
Antidepressants
Antidepressants

• Used in many psychiatric disorders other than


Depression.

• Full clinical response in 6-8 weeks in MDD, up to
6/12 in OCD.


Antidepressants
Remarks Examples Group
Anticholinergic S/E Amitriptyline, nortriptyline Tricyclics
Antihistamine S/E Imipramine & Clomipramine
Adrenergic S/E
As TCA Maprotiline, amoxapine Tetracyclics

Hypertensive crisis* Phenelzine, moclobemide Monoamine


oxidase inhibitors
(MAOIs)

Serotonin syndrome* Sertraline, fluoxetine, paroxetine, SSRI


Sexual S/E fluovoxamien, citalopram
GI disturbances

May ↑BP Venlafaxine SNRI


+ As SSRI’s
Indication of Antidepressants

• Depressive Disturbances
• Affective Disorders
• Obsessive-Compulsive Disorders
• Panic Disorders
• Eating Disorders
• Psychosomatic Disorders
• Posttraumatic Stress Disorder
• Alcohol and Drugs Withdrawal Symptoms
• Pain Syndromes
• Enuresis
• Narcolepsy
Side Effects of Antidepressants

 SSRIs
 TCAs


 Dry mouth

 Constipation
 Headache  Blurred vision
 GI upset  Orthostatic
 Sedation hypotension
 Sexual dysfunction  Sedation
 Anxiety  Conduction
abnormalities
 Confusion
Monoamine Oxidase Inhibitors (MAOI)

• Increases biogenic amines by


inhibiting their degradation
• Should not be taken with foods w/
tyramine
• Examples
– Tranylcypromine ( Parnate )
– Phenelzine ( Nardil )
– Iproniazid ( Marsilid )
Reuptake Inhibitor of Monoamine Oxidase Inhibitor
type A (RIMA)

• Moclobemide – Aurorix 150 mg


• Theoretically should have no food
restriction but did not live up to what
has been thought
Mood stabilizers
What is a mood stabiliser?

• It refers to the ability of a drug to


treat one or both poles of bipolar
disorder without causing a switch
to the other pole.
Mood Stabilizers
• Lithium carbonate.
• Carbamazepine – Tegretol 200mg/tab
• Oxcarbazepine – Trileptal 300 &
600mg
• Depakene – Valproic Acid
• Divalproate sodium – Depakine Chrono
500mg/tab
Lithium
• Bipolar disorders have been treated
with lithium for more than 50 years.
• Lithium is an ion whose mechanism
of action is not certain.
• Has a narrow therapeutic window
(0.6 – 1.2mmol/l)
• Proven teratogenic effect.

• Investigations required before
establishing lithium:
– Thyroid function test.
– Renal function test.
– Pregnancy test.
• Follow up:
– Start with a small dose and adjust
dose according to serum level.
– Serum level every three months or
after any change in dose.
– Always look for and ask about side
effects.
Predictors of response
Predictor of Good response Predictors of Poor response

Greater adherence to treatment Rapid cycling bipolar illness

‘Pure’ form of bipolar illness Paranoid feature

Family history of bipolar illness Substance abuse

Mania followed by depression Poor psychosocial support

Previous good response to Depression followed by mania


treatment
Side effects & Signs of Toxicity
Side Effects Early signs of toxicity Advanced Signs of
Nausea Coarse tremor toxicity
Hyperreflexia
Vomiting Ataxia Hyperextension
Diarrhoea Dysarthria Convulsions
Fine tremor Nystagmus Toxic psychosis
Dry mouth Renal impairment syncope
Polyuria Anorexia oliguria
Polydipsia Muscle weakness Circulatory failure
Vertigo Coma
Weight gain Death
Oedema
Side effects or toxicity, what to do?

• Side effects:
– Decrease dose and follow up for relapse.
– Change mood stabilizer
• Early Toxicity:
– Stop lithium
– Encourage fluid intake (oral +/- I.V)
– Follow up for signs deterioration.
• Late Signs of toxicity:
– Stop lithium.
– I.V fluids/Dialysis
Sodium Valproate
• Anticonvulsant.
• Mood of action as mood stabilizer is
not certain.
• Main side effects:
– Weight gain.
– Hair loss
– Liver impairment.
– Teratogenecity.
Anxiolytics
Benzodiazepines
Long Acting Intermediate Short-acting

Diazepam Midazolam Triazolam

Flurazepam Clonazepam alprazolam

Clorazepate Clobazam
dipotassium
Lorazepam

Estazolam
Antiparkinsonism
Antiparkinsonism
• Biperidin HCl – Akineton 2mg.
• Diphenhydramine – Benadryl 50mg
• Amantadine – Symmetrel 100mg
• Benztropine mesylate – Cogentin
2mg
• Trihexyphenidyl HCl – Artane 2mg


others
Others
• β β λ ο χ κ ε ρ σ

• Cholinesterase inhibitors:
 Donepezil, Rivastigmine,
Galantamine.

• Sympathomimetics:
 Methylphenidate,
Dextroamphetamine.
Prescribing a Psychotropic Agent

• Making a diagnosis
• Choose a medication:
► Family or personal hx of response

► Adverse effects vs. key symptoms

• Starting dose
• Monitor side effects & clinical response
• Adjust dose if needed

Failure of Response; What to do?

• Poor Compliance?

• Wrong Diagnosis?

• Subtherapeutic Dosage?

• Subtherapeutic Duration?

• Substance Abuse?

• Drug-Drug Interaction?