PSYCHOPHARMACOLOGY

Dr Nabeel Ibad
MBBS;FCPS
Head Deptt of Psychiatry
Shaikh Zayed Hosp, Lahore.
 STIGMA
ATTACHED WITH
PSYCHIATRIC
ILLNESS
Society Concepts
1) Depression is illness of rich & Idle people.
2) Depression is a weakness or laziness or
“Drama” or “Makar”.
3) Antidepressant medicines are habit
forming tranquilizers.
4) Medications make your mind slow and
make a person sleepy.
5) Person need to get better using his will
power
 300 MILLION
people
around the world have
DEPRESSION
 PSYCHIATRISTS
&
PSYCHOLOGISTS
Mode of Treatments
Medication

Counselling

ECT
Mechanism of drug action
• Pharmacokinetics
• Absorption
• Distribution
• Metabolism
• Excretion
• Pharmacodynamics
• Half-life
• Efficacy/potency
• Side Effects
Psychotropic medications

• Anti-psychotics
• Anti-depressants
• Anti-anxiety
• Anti-epileptics
• Mood stabilizers
• Neuroleptics
• Tranquilizers
• Major
• Minor
• Psychostimulants
Anti-psychotics
• 1st Generation
• Phenothiazines (include Chlorpromazine, Trifluperazine)
• Butyrophenones (include Haloperidol)
• Thioxanthines (include Flupenthixol & Zuclopenthixol)

• 2nd Generation
• Substituted benzamide (Sulpride, Amisulpride)
• Benzisoxazole (Ripesridone and Ziprasidone)
• Dibenzodiazepine (Olanzapine and Clozapine)
• Dibenzothiazepine (Quetiapine)
• Others eg Aripiprazole, Laurasidone
AntiPsychotics
• Indications
•
• Side Effect Profile

• Mechanism of Action
Typical Anti-psychotics
• Are D2 dopamine receptor antagonists
• High potency typical antipsychotics bind to the D2
receptor with high affinity. As a result they have higher risk
of extrapyramidal side effects
• Examples include:
• Fluphenazine
• Haloperidol
• Pimozide
Atypical Anti-psychotics
• The Atypical Antipsychotics - atypical agents are
serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect
dopamine and serotonin neurotransmission in the four key
dopamine pathways in the brain
• Example include:
• Risperidone
• Olanzapine
• Quetiapine
• Clozapine
Phenothiazine
• Chlorpromazine (Largactil(
• Thioridazine (Melleril)
• Fluphenazine (Modecate)
Butyrophenone
• Haloperidol (Serenace)
Thioxanthenes
• Flupenthixol (Fluanxol)
• Clopenthixol (Clopixol)
Benzisoxazole
• Risperidone (Risperdal)
• Ziprasidone (Zeldox)
Dibenzodiazepine
• Olanzapine (Zyprexa)
• Clozapine (Clozaril)
Dibenzothiazepine
• Quetiapine (Seroquel)
Substituted benzamide
• Sulpiride
• Amisulpiride
Others
• Aripiprazole (Adabilizer)
Risperidone (Risperdal)
• Available in regular tabs, IM depot forms and
rapidly dissolving tablet
• Functions more like a typical antipsychotic at
doses greater than 6mg
• Increased extrapyramidal side effects (dose
dependent)
• Most likely atypical to induce hyperprolactinemia
• Weight gain and sedation (dosage dependent)
Olanzapine (Zyprexa)
• Available in regular tabs, immediate release IM,
rapidly disolving tab, depot form
• Weight gain (can be as much as 30-50 lbs with
even short term use)
• May cause hypertriglyceridemia,
hypercholesterolemia, hyperglycemia (even
without weight gain)
• May cause hyperprolactinemia (< risperidone)
• May cause transaminitis (2% of all patients)
Ziprasidone (Geodon)
• Available regular tabs and IM immediate release
form
• Clinically significant QT prolongation in
susceptible patients
• May cause hyperprolactinemia (< risperidone)
• No associated weight gain
• Absorption is increased (up to 100%) with food
Quetiapine (Seroquel)
• Available in a regular tablet form only
• May cause transaminitis (6% of all patients)
• May be associated with weight gain, though less
than seen with olanzapine
• May cause hypertriglyceridemia,
hypercholesterolemia, hyperglycemia (even
without weight gain), however less than
olanzapine
• Most likely to cause orthostatic hypotension
Clozapine (Clozaril)
• Available in 1 form- a regular tablet
• Is reserved for treatment resistant patients because of
side effect profile but this stuff works!
• Associated with agranulocytosis (0.5-2%) and therefore
requires weekly blood draws x 6 months, then Q- 2weeks
x 6 months)
• Increased risk of seizures (especially if lithium is also on
board)
• Associated with the most sedation, weight gain and
transaminitis
• Increased risk of hypertriglyceridemia,
hypercholesterolemia, hyperglycemia, including
nonketotic hyperosmolar coma and death with and/or
without weight gain
Aripiprazole (Abilify)
• Available in regular tabs, immediate release IM
formulation and depot form
• Unique mechanism of action as a D2 partial
agonist
• Low EPS, no QT prolongation, low sedation
• CYP2D6 (fluoxetine and paroxetine), 3A4
(carbamazepine and ketoconazole) interactions
that the manufacturer recommends adjusted
dosing. Could cause potential intolerability due to
akathisia/activation.
• Not associated with weight gain
Unwanted effects
• Antidopaminergic effects
• Antiadrenergic effects
• Anticholinergiv effects
• Other effects
Antipsychotic adverse effects
• Extrapyramidal side effects (EPS):
• Acute dystonia, Parkinson syndrome, Akathisia

• Tardive Dyskinesia (TD)

• Involuntary muscle movements that may not resolve with drug
discontinuation
• Neuroleptic Malignant Syndrome (NMS):
• Hyperpyrexia
• Muscular rigidity
• Autonomic disturbances
Key pathways affected by dopamine
in the Brain
Dopaminergic pathway
• Meso-limbic
• Meso-cortical
• Nigro-striatal
• Infundibular
• Incerto-hypothalamic
Meso-cortical
• It projects from the ventral tegmentum (brain stem) to
the cerebral cortex. This pathway is felt to be where
the negative symptoms and cognitive disorders (lack of
executive function) arise. Problem here for a psychotic
patient, is too little dopamine.
Meso-limbic pathway
• It projects from the dopaminergic cell bodies in the
ventral tegmentum to the limbic system. This pathway
is where the positive symptoms come from
(hallucinations, delusions, and thought disorders).
Problem here in a psychotic patient is there is too
much dopamine.
Nigro-striatal pathway
• It projects from the dopaminergic cell bodies in the
substantia nigra to the basal ganglia. This pathway is
involved in movement regulation.
• Dopamine suppresses acetylcholine activity.
Dopamine hypoactivity can cause Parkinsonian
movements i.e. rigidity, bradykinesia, tremors),
akathisia and dystonia.
Tubero-infundibular
• It projects from the hypothalamus to the anterior
pituitary.
• Dopamine release inhibits/regulates prolactin release.
Blocking dopamine in this pathway will predispose your
patient to hyperprolactinemia
(gynecomastia/galactorrhea/decreased
libido/menstrual dysfunction).
Antidopaminergic effects
• Acute dystonia
• Akathisia
• Parkinsonism
• Tardive dyskinsea

• Neuroleptic Malignant Syndrome (NMS)

• Hyperpyrexia
• Rigidity
• Autonomic disturbances
Antiadnrenergic effects
• Sedation
• Postural hypotension
• Inhibition of ejaculation
Anticholinergic effects
• Dry mouth
• Reduced sweating
• Urinary hesitancy
• Constipation
• Blurred vision
• Precipitation of glaucoma
Other effects
• Cardiac arrhythmias
• Weight gain and diabetes
• Amenorrhea
• Galactorrhea
• Hypothermia
Antiparkinsonian drugs
• Procyclidine (Kemadrin, Kempro)
Antidepressants
• Mono-amine oxidase inhibitors (MAOIs)
• Tricyclic anti-depressants (TCAs)
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Selective Noradrenaline Reuptake Inhibitors (SNRIs)
• Serotonin receptor agonist (SRAs)
MAOIs
• Phenelzine
• Isocarboxazid
• Tranylcypramine
Monoamine Oxidase Inhibitors (MAOIs)
• Bind irreversibly to monoamine oxidase thereby
preventing inactivation of biogenic amines such
as norepinephrine, dopamine and serotonin
leading to increased synaptic levels.
• Are very effective for depression
• Side effects include orthostatic hypotension,
weight gain, dry mouth, sedation, sexual
dysfunction and sleep disturbance
• Hypertensive crisis can develop when MAOI’s are
taken with tyramine-rich foods or
sympathomimetics.
MAOIs
• Serotonin Syndrome can develop if take MAOI
with meds that increase serotonin or have
sympathomimetic actions. Serotonin syndrome sx
include abdominal pain, diarrhea, sweats,
tachycardia, HTN, myoclonus, irritability, delirium.
Can lead to hyperpyrexia, cardiovascular shock
and death.
• To avoid need to wait 2 weeks before switching
from an SSRI to an MAOI. The exception of
fluoxetine where need to wait 5 weeks because of
long half-life.
TCAs
• Amitryptyline (Amyline)
• Nortryptyline (Sensival)
• Protriptyline

• Imipramine (Tofranil)
• Trimipramine
• Clomipramine (Clomfranil)
Tertiary TCAs
• Have tertiary amine side chains
• Side chains are prone to cross react with other types of
receptors which leads to more side effects including
antihistaminic (sedation and weight gain), anticholinergic
(dry mouth, dry eyes, constipation, memory deficits and
potentially delirium), antiadrenergic (orthostatic
hypotension, sedation, sexual dysfunction)
• Act predominantly on serotonin receptors
• Examples:Imipramine, amitriptyline, doxepin,
clomipramine
• Have active metabolites including desipramine and
nortriptyline
SSRIs
SSRIs
• Fluoxetine (Prozac)
• Fluvoxamine (Faverine)
• Paroxetine (Seroxat)
• Sertraline (Zoloft)
• Citalopram (Cipram)
• Es-Citalopram (Cipralex)
Selective Serotonin Reuptake Inhibitors (SSRIs)
• Block the presynaptic serotonin reuptake
• Treat both anxiety and depressive symptoms
• Most common side effects include GI upset,
sexual dysfunction (30%), anxiety, restlessness,
nervousness, insomnia, fatigue, sedation,
dizziness
• Very little risk of cardiotoxicity in overdose
• Can develop a discontinuation syndrome with
agitation, nausea, disequilibrium and dysphoria
Paroxetine (Seroxat)
• Pros
• Short half life with no active metabolite means no build-
up (which is good if hypomania develops)
• Sedating properties (dose at night) offers good initial
relief from anxiety and insomnia
• Cons
• Significant CYP2D6 inhibition
• Sedating, Weight gain, more anticholinergic effects
• Likely to cause a discontinuation syndrome
Sertraline (Zoloft)
• Pros
• Very weak P450 interactions (only slight CYP2D6)
• Short half life with lower build-up of metabolites
• Less sedating when compared to paroxetine
• Cons
• Max absorption requires a full stomach
• Increased number of GI adverse drug reactions
Citalopram (Cipram)
• Pros
• Low inhibition of P450 enzymes so fewer drug-drug
interactions
• Intermediate ½ life
• Cons
• Dose-dependent QT interval prolongation with doses of
10-30mg daily- due to this risk doses of >40mg/day not
recommended!
• Can be sedating (has mild antagonism at H1 histamine
receptor)
• GI side effects (less than sertraline)
Escitalopram (Cipralex)
• Pros
• Low overall inhibition of P450s enzymes so fewer drug-drug
interactions
• Intermediate 1/2 life
• More effective than Citalopram in acute response and remission
• Cons
• Dose-dependent QT interval prolongation with doses of 10-30mg
daily
• Nausea, headache
Fluvoxamine (Faverin)
• Pros
• Shortest ½ life
• Found to possess some analgesic properties
• Cons
• Shortest ½ life
• GI distress, headaches, sedation, weakness
• Strong inhibitor of CYP1A2 and CYP2C19
Serotonin/Norepinephrine reuptake inhibitors
(SNRIs)
• Inhibit both serotonin
and noradrenergic
reuptake like the TCAS
but without the
antihistamine,
antiadrenergic or
anticholinergic side
effects
• Used for depression,
anxiety and possibly
neuropathic pain
SNRIs
• Venlafaxine (Efexor)
• Duloxetine (Cymbalta)
SRAs
• Mirtazapine (Remeron)
• Trazodone (Deprel)
Anxiolytics
• Used to treat many diagnoses including panic disorder,
generalized Anxiety disorder, substance-related disorders
and their withdrawal, insomnias and parasomnias. In
anxiety disorders often use anxiolytics in combination with
SSRIS or SNRIs for treatment.
Anxiolytics
• Benzodiazepines
• Buspirone
• Etifoxitine

• Antipsychotics
• Antidepressants
Benzodiazepines
• Alprazolam (Xanax(
• Diazepam (Valium)
• Bromazepam (Lexotanil)
• Clonazepam (Rivotril)
• Temazepam (Restoril)
• Clobazam (Frisium)
Benzodiazapines
• Used to treat insomnia, parasomnias and anxiety
disorders.
• Often used for CNS depressant withdrawal
• Side effects/cons
• Somnolence
• Cognitive deficits
• Amnesia
• Disinhibition
• Tolerance
• Dependence
Mood Stabilizers
Anti-epileptics
• Bromide
• Phenobarbitone
• Phenytoin
• Valproic acid
• Carbamazepine
• Lamotrigine
• Levetracetam
• Topiramate
• Gabapentin
• Pregabalin
Antiepileptics
• Carbamazepine (Tegral)
• Na Valproate (Epival)
• Lamotrigine (Lamictal)
• Levetracitam (Lyrica)
• Topiramate (Topamax)
Na channels
• Neurones fire at high frequencies during seizures
• Action potential generation is dependent on Na+ channels
• Na+ channel blockers reduce high frequency firing without
affecting physiological firing
Ca channels
• Absence seizures are caused by oscillations between
thalamus and cortex that are generated in thalamus by T-
type (transient) Ca2+ currents
• Ethosuximide is a specific blocker of T-type currents and
is highly effective in treating absence seizures
K channels

• K+ channels have important inhibitory control over

neuronal firing in CNS – repolarize membrane to end
action potentials
• K+ channels agonists would decrease hyperexcitability in
brain
• So far the only drug with known actions on K+ channels is
valproate
 GABA
GABA
Barbiturates
Benzodiazepines
Gabapentin
Levetiracetam
Tiagabine
Topiramate
Valproate
Vigabatrin

Na++
Na Ca2+2+
Ca
Carbamazepine
Ethosuximide
Lamotrigine
Levetiracetam
Oxcarbazepine
Pregabalin
Phenytoin
Valproate
Topiramate
Valproate
Phenobarbital
• Partial seizures, effective in neonates
• Second-line drug in adults
• Modulator of GABA A receptor
• Half life 50 – 120 hours
• Adverse effects: CNS sedation (excitement) skin rashes
• Tolerance and physical dependence possible
• Interactions: CNS depression with benzodiazepines
Phenytoin
• First line drug for partial seizures
• Inhibits Na+ channels
• Half life 22 – 36 hours
• Adverse affects: CNS sedation, drowsiness, ataxia,
confusion, insomnia, nystagmus, gum hyperplasia,
hirsutism
• Interactions: carbamazepine decreases and diazepam
increases plasma levels
Benzodiazepines
• Diazepam and clonazepam
• Status epilepticus
• GABA A receptors
• Half life: 20 – 40 hours
• Adverse effects: CNS sedative, tolerance, dependence
paradoxical hyper-excitability in children
• Drug interactions: enhance the action of other CNS
depressants
Carbamazepine (Tegral)

• First line agent for acute mania and mania prophylaxis

• Indicated for rapid cyclers and mixed patients
Carbamazepine
• First-line drug for partial seizures
• Inhibits Na+ channels
• Half life: CNS sedation. Agranulocytosis and aplastic
anemia in elderly patients, rare but very serious adverse
side effect. Mild transient leukopenia in 10% (usually
disappears in first 4 months)
• Can exacerbate some generalized seizures
• Drug interactions: stimulates the metabolism of other
drugs and stimulates its own metabolism (this may require
increase in dose)
.
• Before med is started: baseline liver function tests, CBC
and an EKG
• Monitoring: Steady state achieved after 5 days -check 12
hours after last dose and repeat CBC and lfts
• Goal: Target levels 4-12mcg/ml
• Need to check level and adjust dosing after around a
month because induces own metabolism.
Carbamazepine side effects
• Rash- most common SE seen
• Nausea, vomiting, diarrhea, transaminitis
• Sedation, dizziness, ataxia, confusion
• AV conduction delays
• Aplastic anemia and agranulocytosis (<0.002%)
• Water retention due to vasopressin-like effect
which can result in hyponatremia
• Drug-drug interactions
Valproate
• First-line for generalized seizures, partial seizures
• Enhances GABA transmission, blocks Na+ channels,
activates K+ channels
• Half life: 6 – 16 hours
• Adverse effects: CNS depressant , anorexia nausea,
vomiting hair loss, weight gain, elevation of liver enzymes.
Hepatotoxicity is rare but severe
• Drug Interactions: may potentiate CNS depressants
Steven-Johnson syndrome
Valproic acid (Epival)
• Valproic acid is as effective as Lithium in mania
prophylaxis but is not as effective in depression
prophylaxis.
• Factors predicting a positive response:
• rapid cycling patients (females>males)
• comorbid substance issues
• mixed patients
• Patients with comorbid anxiety disorders
• Better tolerated than Lithium
Valproic acid
• Before med is started: baseline liver function tests (LFT),
pregnancy test and CBC
• Start folic acid supplement in women
• Monitoring: Steady state achieved after 4-5 days -check
12 hours after last dose and repeat CBC and Liver
Function Tests
• Goal: target level is between 50-125
Ethosuximide
• Absence seizures
• Blocks T-type Ca++ currents in thalamus
• Half life: 40 hours
• Adverse effects: gastric distress – pain, nausea, vomiting.
Transient fatigue, dizziness, headache
• Drug interactions: Valproate inhibits its metabolism
Lamotrigine
• Effective against generalized seizures
• Mono-therapy for refractory partial seizures
• Add-on therapy
• Inhibition of Na+ channels, glutamate release , may inhibit
Ca++ channels
• Half life: 24 hours
• Adverse effects: CNS sedative (less), Dermatitis
• Drug interactions: Valproate increases its level,
Carbamazepine decreases its level
Lamotrigine ( Lamictal)
• Indications similar to other anticonvulsants
• Also used for neuropathic/chronic pain
• Before med is started: baseline liver function tests
• Initiation/titration: start with 25 mg daily X 2 weeks then
increase to 50mg X 2 weeks then increase to 100mg-
faster titration has a higher incidence of serious rash
• If the patient stops the med for 5 days or more have to
start at 25mg again!
Levetiracetam
• Add-on therapy for partial seizures
• Binds to synaptic vesicle protein SV2A, may regulate
neurotransmitter release
• Half life: 6 – 8 hours
• Adverse effects: CNS depressant
• Drug interactions: minimal
Topiramate
• Effective as monotherapy for partial or generalized
seizures
• Add-on for refractory partial or generalized seizures
• Blockade of Na+ channels, increases frequency of GABA
A channel openings, may interfere glutamate binding
• Half life: 20 – 30 hours
• Adverse effects: CNS sedative
• Drug interactions: some drugs
Antipsychotics as mood stabilizers
Antipsychotics as mood stabilizers
• Olanzapine
• Quetiapine
Lithium
• Salt
• Soft drinks
• Lithium batteries
• Greek tradition
• Therapeutic salt (Cade)
• Mood stabilizer
 Lithium

• Only medication to reduce suicide rate.

• Rate of completed suicide in BAD ~15%
• Effective in long-term prophylaxis of both mania
and depressive episodes in 70+% of BAD I pts
• Factors predicting positive response to lithium
• Prior long-term response or family member with good
response
• Classic pure mania
• Mania is followed by depression
Lithium
• Dose 400 – 800 mg / day
• Serum li level
• 0.5 – 0.8 mmol/L prophylactic
• 0.8 – 1.0 mmol/L therapeutic
• Toxicity
• Hypothyroidism
• Cardiac toxicity
• Diabetes insipidus
Lithium- how to use it
• Before starting :Get baseline creatinine, TSH and
CBC. In women check a pregnancy test- during
the first trimester is associated with Ebstein’s
anomaly 1/1000 (20X greater risk than the
general population)
• Monitoring: Steady state achieved after 5 days-
check 12 hours after last dose. Once stable
check q 3 months and TSH and creatinine q 6
months.
• Goal: blood level between 0.6-1.2
Lithium side effects
• Most common are GI distress including reduced
appetite, nausea/vomiting, diarrhea
• Thyroid abnormalities
• Nonsignificant leukocytosis
• Polyuria/polydypsia secondary to ADH
antagonism. In a small number of patients can
cause interstitial renal fibrosis.
• Hair loss, acne
• Reduces seizure threshold, cognitive slowing,
intention tremor
Lithium toxicity
• Mild- levels 1.5-2.0 see vomiting, diarrhea, ataxia,
dizziness, slurred speech, nystagmus.
• Moderate-2.0-2.5 nausea, vomiting, anorexia, blurred
vision, clonic limb movements, convulsions, delirium,
syncope
• Severe- >2.5 generalized convulsions, oliguria and renal
failure
Barbiturates
• Anxiolytic
• Antidepressant
• Alcohol like withdrawal
• Abrupt withdrawal is dangerous
• Seizures leading to sudden death
Cannabis
• Cannabis sativa
• Marihjuana resins
• Tetrahydrocannabinol (THC)
• Effects
• Mood
• Expectations
• Social settings
• Adverse effects
• Mental illness
• Tolerance
Amphetamines
• ADHD
• Narcolepsy
• Effects
• Mood
• Over-talkativeness
• Insomnia
• Dryness of lips
• Increased heart rate & blood pressure
• psychosis
Amphetamine
• Cardiac effects
• Cardiac arrhythmia
• Hypertension
• Cardio-Vascular Accident
• Circulatory collapse
• Amphetamine induced psychosis
• Withdrawal syndrome (Crash)
Cocaine
• CNS effects
• Excitement
• Euphoria
• Grandiose thinking
• Impaired judgement
• Sexual disinhibition
• Paranoid ideations
• Aggressive behavior
• Formication (Cocaine bugs)
• Cardiac effects
MDMA
• Methylenedioxymethamphetamine
• Positive mental state
• Euphoria
• Sociability
• Intimacy
• Loss of appetite
• Tachycardia
• Bruxism
• Sweating
Cannabis
• Aesthetic experiences
• Distortion of perception
• Red eyes
• Dryness of mouth
• Tachycardia

• No teratogencity
• Anxiety
• Paranoid ideations
• Acute confusional state
Other treatments
• Bright light therapy
• Transcranial Magnetic Stimulation
• Deep brain stimulation
• Vagus nerve stimulation (VNS(
• Psychosurgery
• Sub-caudate tractomy
• Anterior cingulotomy
• Capsulectomy
Bright light therapy
• 2500 1000
• Phototherapy
Transcranial Stimulation
• Magnetic
Psycho-surgery
• OCD