PSYCHOPHARMACOLOGY

AND ECT

Nur Adibah binti Zairul Azman 082019100003

Parameshvarri K N Vaiappuri 082019100014
Nurul Atiqah Akmal binti Rokbi 082019100008
TABLE OF CONTENTS
01. INTRODUCTION 02. MOOD STABILISING
DRUGS

03. HYPNOTICS & ANXIOLYTICS 04. ANTIPSYCHOTICS

05. ANTIDEPRESSANTS 06. ECT

INTRODUCTION

NUR ADIBAH 082019100003

PHARMACOKINETICS
● Absorption - absorbed readily from the intestine
● Metabolism - metabolized partially in the liver to the systemic circulation, known as the
first pass metabolism.
○ Some drugs may induce liver enzymes (e.g. barbiturates) or inhibit them (e.g.
monoamine oxidase inhibitors (MAOIs)).
● Distribution - In plasma, psychotropic drugs are bound to protein. They can pass easily into
the brain due to its lipophilic state
● Excretion - occurs in the kidneys. Lithium is filtered passively in the glomerulus and then
partly reabsorbed in the tubules by the mechanism that absorbs sodium.
DRUG
INTERACTIONS
● Most pharmacokinetic interactions
are at the stage of liver
metabolism.
● However, Lithium is interfered at
the kidneys
● Antagonism occurs between
tricyclics and some
antihypertensive drugs
DRUG WITHDRAWAL
● Tissues adjust to the drugs that have
been given for a long time
● Temporary disturbance of function
occurs when the drug is withdrawn,
appears clinically as a withdrawal
syndrome.
● Anxiolytics and hypnotics may
induce this effect
HOW TO PRESCRIBE PSYCHOTROPIC
DRUGS?
1. Use well-tried drugs
2. Change drugs only for a good reason
3. Combine drugs only for specific indications
4. Adjust dosage carefully
5. Plan the interval between doses
6. Decide the duration of treatment
7. Advise patients
ADVICE TO PATIENTS
1. The initial effects of the drug
2. Delay before therapeutic effects appear
3. First signs of improvement
4. Common side effects
5. Any serious side effects that should be reported immediately
6. Restrictions while drug is taken
7. Duration the patient needs to take the drugs
TYPES OF PSYCHOTROPIC DRUGS
● Psychotropic drugs: drugs that have a significant effect on higher mental functions
○ Anxiolytic drugs - reduce anxiety with calming effect
○ Hypnotics - promote sleep
○ Antipsychotic drugs - control delusions, hallucinations and psychomotor excitement in
psychoses.
○ Antidepressants - relieve the symptoms of depressive disorders, chronic anxiety disorders,
obsessive-compulsive disorder and nocturnal enuresis
○ Mood stabilising drugs - prevent recurrent affective disorder
○ Psychostimulants - elevate mood and for treatment of hyperactivity syndromes in children
IDEAL PSYCHOTROPIC DRUGS
● Can cure underlying pathology causing the disorder
● Able to benefit all the patients suffering from the disorder
● Should have no side effects or toxicity in therapeutic range
● Rapid onset of action
● No dependence and no withdrawal symptoms when stopping the medication
● No tolerance to the drug so same dose can be effective over a period of time
● Not be lethal in overdoses
MOOD STABILISING
DRUGS
NUR ADIBAH 082019100003
➔ Mood Stabilisers: Drugs that prevent recurrence of bipolar disorder and acute mood episodes
➔ The main mood stabilizers are:
◆ Lithium
◆ Sodium valproate
◆ Carbamazepine
◆ Lamotrigine.
 LITHIUM
● An element that was initially used to treat
gout and salt replacement in cardiac
disease
● Later discovered its ability to treat mania
PHARMACOKINETICS
● Lithium is absorbed rapidly from the gastrointestinal tract
● Not protein bound
● Distribution is in total body water with slow entry into intracellular compartment
○ In thyroid (3-5 times serum level)
○ Saliva (2 times)
○ Milk (0.3-1.0)
○ CSF (0.4)
● Excreted by the kidneys where it is filtered and partly reabsorbed.
○ Proximal reabsorption is influenced by sodium balance
○ Depletion of sodium leads to retention, causing high blood lithium level
● Lithium concentrations may rise to dangerous levels during:
○ Dehydration - proximal tubule absorbs more water hence, more lithium is reabsorbed.
○ Sodium depletion - Lithium is carried by the mechanism that carries sodium, and more
lithium is transported when there is less sodium.
○ Thiazide therapy - Thiazide diuretics increase the excretion of sodium but not lithium so,
plasma lithium rises
INDICATIONS & CONTRAINDICATIONS
INDICATIONS
1. Treatment of acute mania
2. Prophylaxis of bipolar mood disorder
3. Treatment of schizoaffective disorder
4. Prophylaxis of unipolar mood disorder
5. Treatment of cyclothymia, acute
depression, chronic alcoholism (with
significant depressive symptoms)
6. Treatment of impulsive aggression
7. Kleine-Levin syndrome
CONTRAINDICATIONS
1. Presence of cardiac, renal, thyroid and
neurological dysfunctions
2. Presence of blood dyscrasia
3. During pregnancy or lactation
4. Administrations of thiazide diuretics,
tetracyclines or anaesthetics
MECHANISM OF ACTION
MECHANISM OF ACTION
● Lithium interferes with the phosphatidyl-inositol cycle by inhibiting the enzyme inositol
monophosphatase, blocking the conversion of IP to free inositol

● The activation of phospholipase C hydrolyses the PIP into diacylglycerol and IP3, which finally
becomes free inositol. Inositol will resynthesis into PIP2.

● DAG is converted into protein ● Inhibition of IP3 will decrease

kinase C that is overactive in Mania. calcium mobilisation from the
Reduction of inositol will decrease intra-cellular pools by ITP
the level of PIP2 and relief (inositol-triphosphate)- dependent
symptoms of acute mania Ca channels.
 TOXIC EFFECTS
● Start to appear over 1.5 mmol/litre
● The drug is often given twice a day.

Therapeutic levels = 0.6-1.2 mEq/L (acute mania)

Prophylactic levels = 0.6-1.0 mEq/L (relapse prevention in
bipolar)
Toxic lithium levels >2.0 mEq/L
SIDE EFFECTS
➔ Polyuria - can lead to dehydration with the risk of lithium intoxication.
◆ Patients are advised to drink enough water to compensate for the fluid loss.
➔ Fine tremors
◆ Most patients adapt to this; for those who do not, propranolol 10 mg three times daily often
reduces the symptom. Coarse tremor is a sign of toxicity.
➔ Enlargement of the thyroid
◆ The thyroid shrinks again if thyroxine is given while lithium is continued, and it returns to
normal a month or two after lithium has been stopped.
➔ Hypothyroidism with a compensatory rise in thyroid stimulating hormone.
➔ Impaired memory.
➔ Long-term effects on the kidney - persistent impairment of concentrating ability, nephrogenic
diabetes insipidus
SIDE EFFECTS
Neurological - Tremors
- Muscular weakness
- Cogwheel rigidity
- Seizures
- Neurotoxicity - delirium, cerebellar signs, involuntary
movements, seizures

Renal - Polyuria, polydipsia

- Tubular changes
- Nephrogenic diabetes insipidus
- Nephrotic syndrome

Cardiovascular - Hypokalemia (T wave depression)

SIDE EFFECTS
Endocrine - Goitre
- Hypothyroidism
- Weight gain

Gastrointestinal - Nausea, vomiting, diarrhea, metallic taste, abdominal pain

Dermatological - Acneiform eruptions

- Papular eruptions

Pregnancy and lactation - Teratogenic

- Toxic in breastfeeding infants
- Ebstein’s anomaly
SIDE EFFECTS
DRUG INTERACTIONS
● ACEi, Angiotensin 2 receptor antagonists, NSAIDS, COX2 inhibitors can increase the risk of
lithium toxicity
● Teratogenesis - Lithium crosses the placenta. The drug should be avoided in the first trimester of
pregnancy.
○ Lithium should be stopped a week before delivery.
○ Lithium is secreted into breast milk so, bottle-feeding is usually advisable.
DRUG INTERACTIONS
MANAGEMENT OF LITHIUM TREATMENT
● Lithium should be withdrawn gradually over a few weeks
● Careful management is essential due to potential effects of therapeutic doses and toxic effects of
lithium on the thyroid and kidneys, and the toxic effects of excessive dosage.
● Lithium is usually continued for at least 2 years
● Before starting lithium:
○ Physical examination - weight and ECG
○ Thyroid function tests, electrolytes and urea
○ Blood creatinine levels
○ Full blood count
○ Pregnancy tests
● Advice to the patient:
○ Common side effects
○ Early toxic effects
○ The need to keep strictly to the dosage prescribed
○ The arrangements for monitoring blood levels of lithium
○ The need to stop the drug and seek medical advice if these conditions arise.
 SODIUM
VALPROATE
- Sodium valproate was first introduced
as an anticonvulsant.
- Later, it was used to control acute
mania and prophylaxis of bipolar
mood disorder
● MOA: Increases GABA and other GABAergic mechanisms
● Pharmacokinetics:
○ Rapidly and completely absorbed after oral administration
○ Peak plasma level reached at 1-4 hours after single oral dose
○ Half life is 8-17 hours
● Usual dosage: 1000-3000 mg/day orally
● Therapeutic blood level: 50-125 mg/ml
INDICATIONS
1. Bipolar disorders (acute mania)
a. Comorbid substance abuse or other psychiatric disorder
b. Late age of onset and shorter duration of illness
c. History of poor response to lithium
d. Dysphoric mania, mixed affective episodes or rapid cycling
e. Organic/complicated mania with seizures, head trauma or EEG abnormalities
f. Depression-Mania-Well Interval (D-M-I) pattern of illness
2. Neurological disorders
a. Migraine and pain syndromes
b. Seizure disorders
3. Other disorders
a. Behavioural agitation in dementia
b. ADHD
c. Schizoaffective disorder
d. Alcohol withdrawal
 SIDE EFFECTS & DRUG INTERACTION
SIDE EFFECTS - Sedation, tiredness, tremor
- Gastrointestinal disturbance
- Reversible hair loss
- Thrombocytopenia
- Menstrual disturbances
- Hepatic toxicity (young children)
- Acute hemorrhagic pancreatitis
- Steven-Johnson syndrome

DRUG ● Valproate increases serum levels of lamotrigine, tricyclic antidepressants and

INTERACTIONS zidovudine
● Drugs (aspirin, ibuprofen, erythromycin) may increase serum levels of valproate.
Others (Carbamazepine, phenytoin and rifampicin) may decrease serum levels of
valproate

TERATOGENICITY Valproate is teratogenic - avoided in pregnant women and used with caution in women of
childbearing potential.
CARBAMAZEPINE
- Carbamazepine was introduced as an
anticonvulsant.
- Later it was found to prevent the
recurrence of affective disorder.
- It is effective in those who are
unresponsive to lithium, and for
rapidly recurring bipolar disorder.
● Dosage and plasma concentration.
○ Usually started at 400 mg daily in outpatients
○ Increased up to 800–1000 mg or higher in inpatients.
○ Long-term treatment: doses depend on tolerability between 200–1600 mg/day orally
INDICATIONS
1. Seizures
a. Complex partial seizures
b. Generalised tonic clonic
c. Alcohol withdrawal seizures
2. Psychiatric disorders
a. Bipolar mood disorder
b. Impulse control disorder and aggression
c. Psychosis (mania) with epilepsy
d. Borderline personality disorder
e. Cocaine withdrawal symptoms
3. Paroxysmal pain syndrome
a. Trigeminal neuralgia
b. Phantom limb pain
 SIDE EFFECTS & DRUG INTERACTION
SIDE EFFECTS - Drowsiness, dizziness
- Nausea and vomiting
- Double vision
- Skin rash, Steven-Johnson syndrome
- Cholestatic jaundice
- Ataxia
- Agranulocytosis
- Bone marrow depression
- Cardiovascular collapse

DRUG ● Carbamazepine can accelerate the metabolism of other drugs

INTERACTIONS ● Reducing the effectiveness of the hormones in the contraceptive pill

TERATOGENICITY ● Carbamazepine should be avoided in pregnancy (cause cleft palate, spina bifida)
and lactation
 LAMOTRIGINE
- Lamotrigine is primarily an
anticonvulsant.
- It may be effective in bipolar
depression and it also prevents
depressive relapse in bipolar disorder.
SIDE EFFECTS & DRUG INTERACTION
● Dosage and plasma concentration.
○ Lamotrigine is started very gradually, initially 25 mg daily for 2 weeks, then 50 mg daily
for 2 weeks, and then further gradual increase.
○ The usual dose in bipolar disorder is 100–300 mg daily
● Adverse effects.
○ Rash
○ Nausea, headache and dizziness
○ Tremor
● Drug interactions.
○ Lamotrigine levels are increased by valproate.
○ The combination of lamotrigine and carbamazepine - cause neurotoxicity.
● Teratogenicity - may increase risks of cleft palate
HYPNOTICS

NUR ADIBAH 082019100003

Benzodiazepines
● Most frequently used
● A short-acting drug (temazepam) can treat initial insomnia.
● The hangover effects can be hazardous for drivers or those who operate machines.
Non-benzodiazepines acting on GABA receptors

● Zopiclone, zolpidem, and zaleplon

● Bind selectively to omega 1 benzodiazepine sites on GABA receptors but not to the omega 2 sites
involved in cognitive functions, including memory.
● Short acting and more preferred than benzodiazepines
● Alcohol potentiates the effects of hypnotic drugs - cause respiratory depression.
○ Chlormethiazole and barbiturates should not be prescribed for patients who drink excessive
amounts of alcohol
● Prescribing for special groups :
○ For children - occasionally for the treatment of night terrors or somnambulism.
○ For the elderly - extra care is required as hypnotics may cause confusion and risk injury
ANXIOLYTICS

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Anxiolytic Drugs
● Buspirone seems to be an exception to the
● Anxiolytic drugs reduce anxiety, and in
general rule that anxiolytics produce
larger doses produce drowsiness (they are
dependency, but its anxiolytic effect develops
sedatives) and sleep (they are also
more slowly and is less intense than that of the
hypnotics)
● benzodiazepines.
Anxiolytics are used most appropriately to
● The drugs called anxiolytics are not the only
reduce severe anxiety.
● ones that reduce anxiety. Antidepressant and
They should be prescribed for a short time,
antipsychotic drugs also have anxiolytic
usually a few days, and seldom for more
properties.
than 2–3 weeks.
● Since they do not induce dependence, they are
● Longer courses of treatment may lead to
sometimes used to treat chronic anxiety.
tolerance and dependence
Benzodiazepines
● These bind to the benzodiazepine-receptor site
on GABAA (gamma-aminobutyric acid)
receptors and thereby potentiate inhibitory
transmission.
● Benzodiazepines have muscle relaxant and
anticonvulsant properties, as well as
anxiolytic, sedative, and hypnotic effects

Clonazepam is most commonest benzodiazepines

used in india
 Benzodiazepines
Side effect
● Mainly drowsiness, with ataxia at larger doses (especially in the elderly).
● These effects, which may impair driving skills and the operation of machinery
● Benzodiazepines can release aggression by reducing inhibitions in people with a tendency to this kind of
behaviour.
● This should be remembered, for example, when prescribing for women judged to be at risk of child abuse, or
anyone with a history of impulsive aggressive behaviour.
Toxic effects
● Benzodiazepine effects can be reversed with the benzodiazepine receptor antagonist flumazenil.
● There is no convincing evidence of teratogenic effects;
● nevertheless, these drugs should be avoided in the first trimester of pregnancy unless there is a strong
indication for their use
 WITHDRAWAL EFFECTS
● It occur mainly due to suddenly stop the drugs from higher dose
● Withdrawal effects occur after benzodiazepines have been prescribed for more
than a few weeks; they have been reported in up to half the patients taking the
drugs for more than 6 months.
● Seizures occur infrequently after rapid withdrawal from large doses.
● The obvious similarity between benzodiazepine withdrawal symptoms and those
of an anxiety disorder makes it difficult, in practice, to decide whether they arise ● Clinically , patient stop the drugs and come to
from withdrawal of the drug or the continuous presence of the anxiety disorder hospital. Doctor should differentiate between
withdrawal sym & anxiety disorder syms.
for which treatment was initiated. ● Most common symptoms of benzodiazepine
● A helpful point is that withdrawal symptoms generally begin 2–3 days after withdrawal is tremors , restlessness, insomnia
withdrawing a short-acting drug, or 7 days after stopping a long-acting one,
and diminish again after 3–10 days. Anxiety symptoms often start sooner and
persist for longer.
● Withdrawal symptoms are less likely if the drug is withdrawn gradually over
several weeks
BUSPIRONE
● This anxiolytic, which is an azapirone, has no affinity for benzodiazepine receptors but stimulates 5-HT1A
receptors and reduces 5-HT transmission.
● It takes about 2-3 weeks before its action is apparent.
● It does not cause sedation but has side effects of headache, nervousness, and lightheadedness.
● It does not appear to lead to tolerance and dependence.
● Its action is slower than that of benzodiazepines and less powerful.
Beta Adrenergic Antagonists
● These drugs do not have general anxiolytic effects but can relieve palpitation and tremor.
● They are used occasionally when these are the main symptoms of a chronic anxiety disorder.
● An appropriate drug is propranolol in a starting dose of 20 mg daily increased gradually to 60 mg to 80 mg
maximum depend on person
● The several contraindications limit the use of these drugs.
● These are asthma or a history of bronchospasm, or obstructive airways disease; incipient cardiac failure or heart
block; systolic blood pressure below 90 mmHg; a pulse rate less than 60 per minute; metabolic acidosis, for
example in diabetes; and after prolonged fasting, as in anorexia nervosa.
● There are interactions with some drugs that increase the adverse effects of beta-blockers.
● Before prescribing these drugs, it is important to find out what other drugs the patient is taking, and consult a work
of reference about possible interactions.

When you give beta blockers you should ask 2 thing

● Whether pt is hypertensive
● Cardiac history
● Asthamatic may induce by beta blockers
ANTIPSYCHOTICS

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● Antipsychotic drugs reduce psychomotor excitement, hallucinations, and delusions occurring in schizophrenia,
mania, and organic psychoses.
● It is also known as
○ major tranquilisers because of their calming effect, or
○ neuroleptics because of their parkinsonian and other neurological side effects. (Antiparkinsonian agents are
sometimes employed to control parkinsonian side effects.)
● What investigation should do before starting antipsychotic ?
○ Check weight
○ Height
○ BMI
○ lipid profile - Preventing patient to put on weight and lead to cholesterol related complication
○ ECG - Antipsychotic may cause variation
○ LFT - LFT abnormalities in patients receiving regular antipsychotics are common but generally mild and
transient
DOPAMINE
● Dopamine has 4 major pathways

○ Mesolimbic pathway - Hyperactivity of dopamine in the mesolimbic pathway mediates positive psychotic
symptoms
○ Mesocortical pathway - Decreased dopamine in the mesocortical pathway responsible for negative
symptoms of schizophrenia
○ Nigrostriatal pathway
■ control motor function
■ Deficiency of dopamine in this pathway can lead to dystonia , parkinsonian symptoms
■ Excess of dopamine in this pathway can lead to hyperkinetic movements such as tics and dyskinesia
○ Tuberoinfundibular pathway
■ Control prolactin secretion
■ Dopamine in this pathway inhibits prolactin release
● Clozapine - Least EPS , MAX weight gain ,
least suicidal tendency
● Atypical antipsychotic drugs is the first
choice for treat schizophrenia
● Side of clozapine - agranulocytosis, seizure ,
myocarditis . Do complete blood count
before giving clozapine
First-generation / typical antipsychotic drugs (FGAs)

● Bind strongly to postsynaptic dopamine D2 receptors.

● First-generation antipsychotics are better for treating positive symptoms of schizophrenia (e.g.,
hallucinations, delusions )
● They also decrease the risk of a repeat episode of psychosis
● Mechanism of Action
○ The first-generation antipsychotics work by inhibiting dopaminergic neurotransmission; their
effectiveness is best when they block about 72% of the D2 dopamine receptors in the brain.
○ They also have noradrenergic, cholinergic, and histaminergic blocking action.
When you giving any psychotropic drugs, you should warn the
patient regarding postural hypotension

If you give psychotropic drugs to elderly patient without any

warning , morning they will fall. This put you in trouble.

When you prescribe psychotropic drugs , ask patient to drink

more water and advice to get up slowly. So, sympathetic system
will custom to that.
Second-generation / atypical antipsychotic drugs (SGAs)

● Bind to dopamine D2 , 5-HT2, alpha1-adrenergic, and muscarinic receptors.

● SGAs are less likely to cause movement disorders than the typical antipsychotics and do not cause
hyperprolactinemia.
● SGAs include clozapine, olanzapine, risperidone, quetiapine, sertindole, zotepine, and ziprasidone
● Second-generation antipsychotics treat both positive symptoms and negative symptoms of schizophrenia
● Mechanism of Action
○ Second-generation antipsychotics work by blocking D2 dopamine receptors as well as serotonin receptor
antagonist action. 5-HT2A subtype of serotonin receptor is most commonly involved.
Adverse Effects

● Antidopaminergic effects give rise to four kinds of extrapyramidal symptoms and signs
○ Acute dystonia
○ Akathisia
○ Parkinsonian effects
○ Tardive dyskinesia
Acute Dystonia
● Acute dystonia occurs soon after the treatment
begins.

● Acute dystonia can be controlled by an

anticholinergic drug such as biperiden, given
carefully by intramuscular injection
 Akathisia ( motor & inner restlessness)
● It is an unpleasant feeling of physical restlessness and a need to move, leading to inability to keep still.
● It starts usually in the first 2 weeks of treatment but can be delayed for several months.
● The symptoms are generally disappear if the dose is reduced

FOOT TAPPING
Parkinsonian effects
● Most frequent of the extrapyramidal side effects.
● The syndrome often takes a few weeks to appear.
● Parkinsonism can sometimes be controlled by lowering the dose.
● If this cannot be done without losing the therapeutic effect, an
antiparkinsonian drug can be prescribed.
● With continued treatment, parkinsonian effects may diminish even
though the dose of the antipsychotic stays the same.
● It is appropriate to check at intervals that the antiparkinson drug is
still required, since these compounds may increase the risk of
tardive dyskinesia.
Tardive dyskinesia

● Characteristically a late complication of antipsychotic

treatment.
● The condition may be due to supersensitivity of dopamine
receptors resulting from prolonged dopamine blockade.
● Since it does not always recover when the antipsychotic drugs
are stopped, and responds poorly to treatment, prevention is
important.
● Usually, the best treatment for tardive dyskinesia is to stop
the antipsychotic drug
● At first the dyskinesia may worsen, but often it improves after
several drug-free months. If the condition does not improve, or if
the antipsychotic drug cannot be stopped, an additional drug can
be prescribed in an attempt to reduce the dyskinesia

Foot tapping also seen in tardive dyskinesia

ANTIDEPRESSANTS

PARAMESHVARRI 082019100014
● Depression mainly occurs due to decrease monoaminergic activity within brain.(5-
hydroxytryptamine(serotonin), noradrenaline)
● Antidepressant drugs increase the monoamines 5-HT and/or noradrenaline (NA)
● Drugs with antidepressant are divided conveniently into
○ Specific serotonin reuptake inhibitors (SSRIs)
○ Tricyclic antidepressants (TCA)
○ Serotonin (5-HT) and noradrenaline reuptake inhibitors (SNRIs)
○ Specific noradrenaline uptake inhibitors (NARIs)
○ Monoamine oxidase inhibitors (MAOIs)
● Most antidepressants have a long half-life and so can be given once a day.
● Antidepressants should be withdrawn slowly, because sudden cessation may lead to restlessness,
insomnia, anxiety, and nausea
 Specific serotonin reuptake inhibitors (SSRIs)
● These drugs selectively inhibit the reuptake of serotonin
(5-HT) into presynaptic neurons.

● They are not sedating

● SSRIs may induce suicidal thoughts or behaviour in some

patients, particularly younger people.

● It is important to monitor all patients who start

antidepressant drugs of any kind for the emergence of
suicidal thoughts.
 SSRI
Fluoxetine

Fluvoxamine

Paroxetine

Sertraline
Specific serotonin reuptake inhibitors (SSRIs)
Drug interactions
● The combination of SSRIs with MAOIs should be avoided since the combination may
produce a 5-HT toxicity syndrome with hyperpyrexia, rigidity, myoclonus, coma, and
death.
● Lithium and tryptophan also increase 5-HT function when given with SSRI
● This combination can be useful clinically but needs to be closely monitored. Combinations
of lithium and SSRIs are effective for depressive disorders resistant to other treatment.

Toxic effects
● Overdosage leads to vomiting, tremor, and irritability.
Serotonin and noradrenaline reuptake inhibitors (SNRIs)

● SNRIs works by inhibiting reuptake of serotonin

via inhibition of serotonin transporter and it also
inhibit norepinephrine transporter
● This results in increase level of both serotonin and
norepinephrine which can bind to the postsynaptic
receptors
● SNRI used for depression , anxiety and panic
disorders, pain caused by neuropathy
 SNRI
Duloxetine
Venlafaxine
Sibutramine
Levomilnacipran
 Tricyclic antidepressants
● Tricyclic antidepressants drugs are so named because
their chemical structure has three benzene rings
● TCA primarily inhibit serotonin and norepinephrine
by blocking both of transporter
● Desipramine are more selective inhibitors of
norepinephrine then serotonin transporter
● TCA also inhibit other receptors like alpha receptors ,
histamine receptors and muscarinic receptors
● However, blockage of other receptors is thought to be
responsible for their side effects more than their
antidepressant activity
 TCA
Amoxapine
Amitriptyline
Clomipramine
Desipramine
Doxepin
Imipramine
Treatment for TCA toxicity is the
administration of sodium bicarbonate infusion
 Monoamine oxidase inhibitors
● Monoamine oxidase is a mitochondrial enzyme that degrades monoamines such as serotonin and norepinephrine
● MAOI classified into subtypes A and subtypes B
● MAOI subtype A preferentially metabolizes serotonin but will also metabolize norepinephrine and dopamine
while MAOI subtype B preferentially metabolizes dopamine
● MAOI subtype A is thought to be responsible for antidepressant effects of majority of MAOI
● Primary mechanism of action of MAOI inhibit the activity of MAO enzymes preventing breakdown of
monoamine neurotransmitters and ultimately increase their availability
● MAOI always will be last choice of drugs due to high incidence of drug - drug interaction but also drug food interaction
 MAOI
Phenelzine
Isocarboxazid
Tranylcypromine
Selegiline( selective inhibitor of MAO subtype B)
Interactions with Tyramine and MAOI
● MAO enzymes present in gut. It play important role in breakdown of monoamines ingested in food
● The problem arises when inhibited MAO enzymes cannot metabolize tyramine which contained in foods that
have been fermented
● In synaptic nerve terminal , the tyramine is built up which it acts as a catecholamine releasing agent
● Blood pressure rises substantially with a so-called hypertensive crisis and, occasionally, a cerebral
haemorrhage , followed by stroke
● The release of large amount of catecholamine caused by tyramine leads to hypertensive crisis and potentially
causes stroke
● An important early symptom of such a crisis is a severe, usually throbbing headache.
● Some foods and drinks contain tyramine, a substance that is normally inactivated in the body by monoamine
oxidases.
● Educate patient that they have to avoid tyramine rich foods
 COGNITION
ENHANCING DRUGS
NURUL ATIQAH AKMAL 082019100008
Anticholinesterase (AChE) Inhibitors
❖ These drugs, including donepezil, rivastigmine, and galantamine, increase the function of
acetylcholine, which can improve cognitive functioning, and they are used in the treatment of
Alzheimer’s disease.
❖ On average, they have a modest beneficial effect that might persist for a number of months but
they do not halt or reverse the disorder.
❖ These drugs are used following assessment in a specialist clinic, including tests of cognitive,
global, and behavioural functioning and assessment of activities of daily living.
❖ The main adverse effects include anorexia, nausea, vomiting, and diarrhoea.
 ECT
(ELECTROCONVULSIVE
THERAPY)
NURUL ATIQAH AKMAL 082019100008
Brief History
Cerletti and Bini APA Task Force
Electroshock Redefined the
(electroconvulsive indications and
therapy) guidelines

1934 1938 1970-1976 1990 2001

Von Meduna APA Task Force APA Task Force

Cardiazol (metrazol) Widespread criticism The most recent
induced seizures and modifications version of this task
force
Introduction
❖ In ECT, an electric current is applied
to the skull of an anaesthetized patient
to produce seizure activity while the
consequent motor effects are
prevented with a muscle relaxant.
❖ The electrodes which deliver the
current can be placed with one on
each side of the head (bilateral ECT)
or with both on the same side
(unilateral ECT).
Indications
1. Major severe depression
2. Severe catatonia (non-organic)
3. Severe psychoses (schizophrenia or mania)
4. The 1990 APA Task Force on ECT also defined as suggestive indications (for occasional use) the
following disorders:
a. Organic mental disorders (e.g. organic mood syndrome, organic hallucinosis, organic
delusional disorder, and delirium).
b. Medical disorders (e.g. organic catatonia, neuroleptic malignant syndrome and
parkinsonism).
Indications
❏ The use of ECT in mania and schizophrenia is not a treatment of first choice.
❏ A history of good response with ECT and patient preference for ECT also determine the use of
ECT.
 Severe catatonia (non- Severe psychoses
Major severe depression
organic) (schizophrenia or mania)

I. With suicidal risk (This is the first I. With risk of suicide, homicide or
and most important indication for danger of physical assault
ECT)
II. With very prominent depressive
II. With melancholia features (e.g. schizo-affective
III. With psychotic features disorder).

I. With stupor
II. With poor intake of food and fluids
III. Where speedier recovery is needed.

I. With unsatisfactory response to drug therapy

II. Where drugs are contraindicated, or have serious side-effects.
Pre-treatment Evaluation
1. An informed consent, taken from the patient. If the patient does not have capacity or competence
to give consent, consideration must be given to the most recent legal guidelines and local
procedures which can include the best interest decision with consent of guardian/family and
additional opinion from another professional.
2. Detailed medical and psychiatric history taking, which includes the current and past treatment
history.
3. General and systemic physical examination.
4. Routine laboratory investigations.
5. Examination of fundus oculi to rule out papilloedema.
Contraindications
Absolute
The only absolute contraindication is the presence of raised intracranial tension (so an examination of
the fundus oculi is an essential step). However, the APA Task Force Report on ECT recognises this too as
a relative contraindication.
Relative
These include:
1. Recent myocardial infarction (MI)
2. Severe hypertension
3. Cerebrovascular accident (CVA)
4. Severe pulmonary disease
5. Retinal detachment, and
6. Pheochromocytoma.
Types of ECT
According to techniques;

Direct ECT
● It is administered in the absence of muscular relaxation and general anaesthesia. All the other
steps are the same as in modified ECT. This method of treatment is nowadays very infrequently
used and not understandably encouraged by most guidelines.
Modified ECT
● It is modified by drug-induced muscular relaxation and general anaesthesia administered by an
anaesthetist.
Types of ECT
According to placement of electrodes;
Unilateral ECT
● Electrodes are placed on one side of head,
usually the non-dominant side (right side of
head in right-handed individual).
● Results in less memory impairment but may be less effective than bilateral ECT.
Bilateral ECT

● This is the standard form of ECT used most commonly.

● Each electrode is placed 2.5-4.0 cm above the midpoint, on a line joining the tragus of the ear and
the lateral canthus of the eye.
● It is therefore preferred when a rapid response is essential, or when unilateral ECT has not been
effective.
Techniques for Administration
➔ ECT is usually administered in the morning after an overnight fast.
➔ If given at any other time during the day, the patient should be empty stomach for at least 4 hours.
➔ No oral medication should be given in the morning.
➔ The bladder and bowel should be emptied just before the treatment, as incontinence can occur
during the induced seizure.
➔ Remove dentures, tight clothing, metallic and sharp objects.
➔ The usual anaesthetic precautions are taken.
➔ The patient is placed on a hard bed which is well insulated.
➔ A slow IV drip may be started, though not needed in all patients.
Techniques for Administration
Drugs given;
➔ Atropine (0.6 mg) IV / IM / SC is given 30 minutes before treatment.
➔ Atropine is given to decrease the oral secretions and to prevent vagal stimulation during ECT
which can cause cardiac arrest.
➔ Anaesthetic agent eg propofol (0.75–2.5 mg/kg) or thiopentone (2-5 mg/kg, usually
individualised dose for each patient)
➔ Muscle relaxant like succinylcholine (0.5-1.5 mg/kg)
➔ Succinylcholine is a depolarising blocking agent.
➔ Anaesthetic mask is placed on face and ventilation with 100% oxygen
Techniques for Administration
➔ Succinylcholine administration is followed by
muscular fasciculations which move from above downwards.
➔ When the fine twitching movements disappear from the lower extremities, it is the time of
complete muscular relaxation.
➔ A mouth gag is inserted between teeth, to prevent tongue bite during convulsion and pressure is
applied on mandible to approximate upper and lower teeth till convulsions stop.
➔ The electrodes are moistened with saline or 25% bicarbonate solution.
➔ One attendant places one hand each on both thighs near the knee joint, while another attendant
holds the shoulders.
➔ This is to prevent falls from the bed and causation of fracture or dislocation due to muscular
contractions.
Techniques for Administration
The therapeutic adequacy of the treatment is usually gauzed by the occurrence of a generalized tonic-
clonic seizure lasting for not less than 25-30 seconds.
This is ensured by:
1. Observing the seizure (in direct ECT).
2. EEG recording during ECT (in modified ECT).
3. Occluding the circulation of one extremity with a BP apparatus cuff, before giving
succinylcholine. Thus, the whole body is paralyzed but one extremity convulses and can be
directly observed.
4. Observing plantar extension and eyelid contractions which may be seen despite the muscular
relaxation (not a very reliable method).

**Most guidelines recommended that seizure activity by EEG of at least 25 seconds and observed
convulsion of at least 15 seconds was needed for the seizure to be classified as adequate.
Techniques for Administration
➔ After seizure, the mouth gag is removed, secretions are removed by a suction machine from the
oral cavity, and oxygen mask is applied.
➔ Till consciousness is regained, the patient is turned to one side to prevent aspiration.
➔ The vital parameters are constantly monitored till recovery occurs.
➔ The patient is made to rest, for about 30 minutes to 1 hour, on bed after the treatment is over.
MOA
❏ ECT affects catecholamine pathways between diencephalon (seizure generalisation occur) and
limbic system (for mood disorder) and also involving hypothalamus
❏ Increases threshold for further seizure
❏ Down regulation of B1 receptors in cortex and hippocampus
❏ The beneficial effect, which depends on the cerebral seizure, not on the motor component, is
thought to result from neurotransmitter changes, probably involving 5-HT and noradrenaline
transmission. ECT acts more quickly than antidepressant drugs, although the outcome after 3
months is similar.

(‘jumpstart the brain’ and help to boost the neurotransmission)

Duration of Therapy
➢ The total duration and number of treatments given depends on the diagnosis, presence of side
effects, and the response to treatment.
➢ Usually 6-10 treatments are sufficient, although up to 15 treatments can be given if needed. The
treatments should be spaced, so that no more than 3 ECTs are given per week. Response begins
usually after 2 or 3 treatments; if there has been no response after 6 to 8 treatments, it is unlikely
that more ECT will produce useful change.
➢ Although ECT is very effective in severe depressive disorder, the benefit lasts only till the ECTs
are given. There is no residual benefit after the treatment is over. Hence, the patient needs
antidepressants during and after the ECTs are over.
➢ The usual dose for obtaining an adequate seizure response is 90-150 volts (average 110 volts) for
0.1-1.0 seconds (average 0.6 seconds).
Side Effects
1. Deaths during ECT are usually due to the general anaesthesia, succinylcholine or drug-
interactions.
2. Memory disturbances (both anterograde and retrograde) are very common. These are usually mild
and recovery occurs within 1-6 months after treatment.
3. Confusion may occur in the postictal period. Like memory disturbances, confusion is much
commoner with bilateral ECTs. Usually, no treatment is needed. Parenteral diazepam may be
given for excitement during this period.
4. Other side effects; headache, prolonged apnoea (due to muscle relaxants), prolonged seizure,
cardiovascular dysfunction, emergent mania, muscle aches and apprehension, injury to the teeth,
tongue, or lips.
5. ECT does not cause any brain damage.
Mortality of ECT
❖ The death rate from ECT is about 4 per 100 000 treatments, closely similar to that of an
anaesthetic given for any minor procedure to a similar group of patients.
❖ Mortality is greater in patients with cardiovascular disease, and due usually to ventricular
fibrillation or myocardial infarction.
ONE FLEW OVER THE
CUCKOO’S NEST
SPECIAL GROUPS

NURUL ATIQAH AKMAL 082019100008

Children
❖ Most childhood psychiatric disorders are treated without medication.
❖ Many drugs that are licensed for use in adults have not been adequately studied in children.
❖ When drugs are required, care must be taken in selecting the appropriate dose.
❖ Usually, medication will have been started by a specialist who will advise about continuing
treatment.
Elderly Patients
❖ These patients are often sensitive to drug side effects and may have impaired renal or hepatic
function.
❖ It is important to start with low doses and increase to about half the adult dose in appropriate
cases.
Pregnant women
❖ Psychotropic drugs should be avoided if possible during the first trimester of pregnancy because
of the risk of teratogenesis.
❖ If medication is needed for a woman who could become pregnant, advice is given about
contraception.
❖ If the patient is already pregnant and medication is essential the manufacturer’s advice should be
followed and the risks discussed with the patient.
❖ If the patient becomes pregnant while taking a psychotropic drug the risk of relapse should be
weighed against the reported teratogenic risk of the drug.
❖ In general, it is safer to use long-established drugs for which there has been ample time to
accumulate experience about safety.
Mothers who are breast-feeding
❖ Psychotropic drugs should be prescribed cautiously to women who are breast-feeding because
these pass into breast milk and the possibility is not ruled out that they may affect brain
development.
❖ Some authorities recommend that women receiving psychotropic medication should not breast-
feed. Others continue treatment cautiously with careful monitoring of the baby.
❖ Benzodiazepines pass readily into breast milk, causing sedation.
❖ Most neuroleptics and antidepressants pass rather less readily into the milk; sulpiride, doxepin,
and dothiepin are secreted in larger amounts and should be avoided.
❖ Lithium carbonate enters milk freely and breast-feeding should be avoided.
Patients with concurrent medical illness
❖ Special care is needed in prescribing for patients with medical illness, especially liver and kidney
disorders, which may interfere with metabolism and excretion of drugs.
❖ Conversely, medical disorders may be exacerbated by the side effects of some psychotropic drugs.
❖ For example, cardiac disorder and epilepsy may be affected adversely by some antidepressant
drugs, while drugs with anticholinergic side effects exacerbate glaucoma and may provoke
retention of urine.
References
● Niraj Ahuja’s A Short Textbook of Psychiatry, 7th Edition.
● Psychiatry Oxford, 4th Edition.
THANKS
!

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