Drugs

used in
Psychiatric
disorders

JISS JOHN FRANCIS

 PSYCHIATRIC
DISORDERS
1. Organic mental disorders
2. Psychoses
3. Neuroses
4. Personality disorders
Organic Mental Disorders (Neurocognitive Disorders)
These disorders are characterized by a decline in cognitive function due to a medical or physical condition
affecting the brain. An organic cause is present in these disorders, i.e., there is a definite toxic, metabolic,
pathological change. E.g.: Delirium (substance intoxication), Dementia (Alzheimer's disease-amyloid
plaques)

Psychoses
Psychoses are severe mental disorders characterized by a disconnection from reality. Symptoms often
include delusions, hallucinations, and disorganized thinking. Patients have no insight into these
abnormalities, they are not aware. E.g.: Schizophrenia, paranoia, affective disorders

Neuroses
Neuroses, or neurotic disorders, are a category of mental health conditions characterized by chronic distress
but do not involve a break from reality (as seen in psychoses). Individuals with neuroses experience
significant discomfort and impaired functioning, but they maintain a grasp on reality. E.g.: Anxiety, Fears,
Depression

Personality Disorders
Personality disorders are enduring patterns of behavior, cognition, and inner experience that deviate
markedly from the expectations of the individual's culture. These patterns are pervasive and inflexible,
leading to distress or impairment. E.g.: Paranoid, schizoid, antisocial, histrionic, avoidant, dependent, OCDs.
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Topics we will

cover
• Antipsychotics
• Antianxiety
• Antidepressants
• Mood stabilizers
• CNS Stimulants
1
ANTIPSYCHOTIC Aka Neuroleptics

S
Antipsychotics are a class of medication primarily used to manage
psychosis, including delusions, hallucinations, and disorders like
schizophrenia. They are also used for bipolar disorder, severe
depression, and other mental health conditions.
 Positive symptoms: Delusion, hallucinations
Negative symptoms: poor conc, social withdrawal, poverty of speech, lack of energy
Types
• Typical Antipsychotics (First-Generation)
• Developed in the 1950s, these drugs mainly target dopamine
receptors and are effective in treating positive symptoms of psychosis,
such as hallucinations and delusions.

• Atypical Antipsychotics (Second-Generation)

• Introduced in the 1990s, atypical antipsychotics target both dopamine
and serotonin receptors. They are effective in treating both positive
and negative symptoms of psychosis and are associated with a lower
risk of extrapyramidal side effects.
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 First generation/ Classical/ Typical neuroleptics
Second generation

Phenothiazines Butyrophenones Thioxanthene's Atypical

• Chlorpromazine • Haloperidol • Thiothixene • Clozapine
• Triflupromazine • Droperidol • Chlorprothixene • Olanzapine
• Thioridazine • Trifluperidol • Flupenthixol • Quetiapine
• Mesoridazine • Penfluridol • Zotepine
• Trifluoperazine • Risperidone
• Fluphenazine • Ziprasidone
• Amisulpride
• Remoxipride
• Sertindole
• Aripiprazole

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First generation neuroleptics
Primary Mechanism: Dopamine D2 Receptor Antagonism

Dopamine Receptors: Typical antipsychotics primarily block dopamine D2 receptors in the brain. This
blockade reduces the effects of dopamine, which is thought to be overactive in conditions like
schizophrenia.
Effect on Symptoms: The reduction in dopamine activity in the mesolimbic pathway helps alleviate
positive symptoms of schizophrenia, such as hallucinations and delusions.
Side Effects: However, dopamine antagonism in
other pathways leads to side effects. For example,
blocking dopamine in the nigrostriatal pathway
causes extrapyramidal symptoms (EPS), such as
tremors and rigidity. Long-term use can lead to
tardive dyskinesia. Blocking dopamine in the
tuberoinfundibular pathway can cause increased
prolactin levels, leading to galactorrhea and
gynecomastia.
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9
 CNS: Behavioural effects in normal subjects CPZ reduces motor activity,
produces drowsiness and indifference to surroundings. In psychotic agitated

PHARMACOLOGICAL ACTIONS
patients, it reduces aggression, initiative and motor activity, relieves anxiety and
brings about emotional quietening and drowsiness. It normalizes the sleep
disturbances characteristic of psychoses.

Other CNS Actions:

1. Cortex: CPZ lowers seizure threshold and can precipitate convulsions in
untreated epileptics.
2. Hypothalamus: CPZ decreases gonadotrophin secretion and may result in
amenorrhea in women. It increases the secretion of prolactin resulting in
galactorrhea and gynecomastia.
3. Basal ganglia: CPZ acts as a dopamine antagonist and therefore results in extra
pyramidal symptoms (EPS) (drug induced parkinsonism).
4. Brainstem: Vasomotor reflexes are depressed leading to a fall in BP.
5. CTZ: Neuroleptics block the dopamine receptors in the CTZ and thereby act as
antiemetics. 10
 Autonomic nervous system: CPZ has anticholinergic properties which leads to

PHARMACOLOGICAL ACTIONS
side effects like dryness of mouth, blurred vision, reduced sweating, decreased
gastric motility, constipation and urinary retention. The degree of anticholinergic
activity also varies with each drug.

 CVS: Neuroleptics produce orthostatic hypotension due to alpha blockade action

and reflex tachycardia. CPZ also has a direct myocardial depressant effect like
quinidine.

 Local anesthetic: CPZ has local anesthetic properties, but is not used for the
purpose since it is an irritant.

 Kidney: CPZ depresses ADH secretion and has weak diuretic effects. Tolerance
develops to the sedative and hypotensive actions while no tolerance is seen to
the antipsychotic actions.
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1. Metabolic Side Effects
Weight Gain: Common with many atypical antipsychotics.
Hyperglycaemia: Elevated blood sugar levels, which can lead to diabetes.
Dyslipidaemia: Abnormal cholesterol and triglyceride levels, increasing the risk of cardiovascular
disease.

2. Cardiovascular Effects
QT Prolongation: Prolonged QT interval on ECG, which can lead to arrhythmias (irregular heartbeats).
Drugs like Ziprasidone and Thioridazine are particularly associated with this risk.
Orthostatic Hypotension: A drop in blood pressure upon standing, causing dizziness or fainting.

3. Hormonal and Endocrine Effects

Hyperprolactinemia: Elevated prolactin levels leading to galactorrhoea, gynecomastia, and
menstrual irregularities. This is more common with typical antipsychotics and Risperidone.

4. Anticholinergic Effects: Dry Mouth, Constipation, Blurred Vision, Urinary Retention

5. Sedation and Cognitive Effects
Sedation: Drowsiness and lethargy ADVERSE EFFECTS
Cognitive Blunting: Impaired concentration and memory. 12
6. Neurological Effects
Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening condition characterized by
fever, severe muscle rigidity, altered mental status.

7. Extrapyramidal Symptoms (EPS)

Definition: Extrapyramidal symptoms (EPS) are drug induced movement disorders that include
various types of involuntary movements and muscle control problems.
1. Acute Dystonia: Sudden, sustained muscle contractions, causing twisting, repetitive movements,
or abnormal postures. Can include torticollis (twisting of the neck), oculogyric crisis (upward
deviation of the eyes), and laryngospasm (throat spasm).
2. Akathisia: A state of inner restlessness and a compelling need to be in constant motion. Feeling
of unease, inability to sit still, pacing, fidgeting.
3. Parkinsonism: Symptoms similar to Parkinson's disease, caused by dopamine blockade in the
brain. Bradykinesia (slowness of movement), rigidity, tremors, and shuffling gait.
4. Tardive Dyskinesia: A potentially irreversible condition characterized by repetitive, involuntary
movements, often of the face and tongue. Grimacing, tongue protrusion, lip smacking, rapid eye
blinking. ADVERSE EFFECTS
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Second generation neuroleptics
Primary Mechanism: Dopamine D2 Receptor Antagonism and Serotonin 5-HT2A
Receptor Antagonism
Dopamine Receptors: Like typical antipsychotics,
atypical antipsychotics also block dopamine D2
receptors, but they tend to have a lower affinity for these
receptors, reducing the risk of EPS.

Serotonin Receptors: Atypical antipsychotics

block serotonin 5-HT2A receptors. This action is
thought to mitigate some of the side effects
associated with dopamine antagonism,
particularly EPS. Serotonin antagonism in the
prefrontal cortex is also believed to improve
negative symptoms (e.g., social withdrawal, lack
of motivation) and cognitive deficits associated
with schizophrenia.
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CLOZAPINE OLANZAPINE QUETIAPINE
• Characteristics: Highly • Characteristics: Effective • Characteristics: Used for
effective for treatment for schizophrenia and schizophrenia, bipolar
resistant schizophrenia; bipolar disorder; high risk disorder, and major
requires regular blood of weight gain and depressive disorder; low
monitoring for
agranulocytosis.
metabolic issues; potent risk of EPS; sedating
• Advantages: sedative properties. properties.
Superior
efficacy in treatment-
resistant cases, lower risk • Advantages: High efficacy • Advantages: Low risk of
of EPS, may reduce in managing both positive EPS, effective for various
suicidal behavior in and negative symptoms, psychiatric conditions, can
schizophrenia. low risk of EPS. help with sleep.
• Disadvantages: Risk of
agranulocytosis, sedation, • Disadvantages: Significant • Disadvantages: Weight
weight gain, metabolic weight gain, metabolic gain, metabolic syndrome,
syndrome, risk of seizures. syndrome, sedation. sedation, risk of
orthostatic hypotension.

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RISPERIDONE ZIPRASIDONE ARIPIPRAZOLE

• Characteristics: Effective • Characteristics: Effective • Characteristics: Partial

for schizophrenia, bipolar for schizophrenia and agonist at dopamine D2
disorder, and irritability in bipolar disorder; lower receptors; effective for
autism; higher risk of EPS risk of metabolic side schizophrenia, bipolar
disorder, and major
at higher doses; can effects; must be taken depressive disorder; lower
increase prolactin levels. with food. risk of weight gain and
• Advantages: Effective for • Advantages: Lower risk of metabolic side effects.
positive and negative weight gain and • Advantages: Lower risk of
symptoms, available in metabolic syndrome, low weight gain and metabolic
long-acting injectable risk of EPS. syndrome, low risk of EPS,
form. • Disadvantages: QT can be used as an adjunct in
• Disadvantages: Increased interval prolongation (risk major depressive disorder.
prolactin levels, weight of arrhythmias), sedation, • Disadvantages: Can cause
gain, risk of EPS must be taken with food akathisia (restlessness),
insomnia, gastrointestinal
(especially at higher for proper absorption. problems, partial agonist
doses), metabolic mechanism may not be as
syndrome. effective in some patients.

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2 ANTIANXIE
TY
Aka Anxiolytics

Antianxiety drugs, also known as anxiolytics, are a class of

medications designed to reduce anxiety and treat symptoms
of anxiety disorders. These drugs work by affecting
neurotransmitters in the brain to promote relaxation, reduce
tension, and alleviate symptoms of anxiety.
Drugs used as
Antianxiety
Benzodiazepines: Diazepam, Chlordiazepoxide,
Lorazepam, Alprazolam

5-HT agonist antagonists: Buspirone, Gepirone,

Ipsapirone
Autonomic symptoms of anxiety-tremors, palpitation, hypertension-public
Beta-blockers: Propranolol speaking and performance.

Others: Hydroxyzine
Antihistaminic with anxiolytic property-not preferred due to sedation
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BUSPIRONE
• Buspirone is an azapirone with good anxiolytic properties.
• It is a selective 5-HT partial agonist and binding of buspirone inhibits the release of 5-
HT.
• Buspirone is also a weak D₂ antagonist. It is useful in mild to moderate anxiety.
Antianxiety effect develops slowly over 2 weeks.
• Unlike diazepam, it is not a muscle relaxant, not an anticonvulsant, does not produce
significant sedation, tolerance or dependence and is not useful in panic attacks.
• Buspirone is rapidly absorbed and metabolized in the liver.
• Dose: 5-15 mg.
• Side effects are mild including headache, dizziness, nausea, tachycardia, nervousness
and rarely restlessness.
• Uses: Buspirone is used in mild to moderate anxiety and is particularly beneficial when
sedation is to be avoided.
• Ipsapirone and gepirone are similar to buspirone.
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3
ANTIDEPRESSAN
TS
Antidepressants are a class of medications used to treat depression
and other mood disorders.
Depression could be:
Due to stressful and
distressing
circumstances in life

Reactive
Biochemical abnormality
Unipolar in brain- deficiency of
Endogenous monoamine
Depression
Mania & depression
Bipolar
alternate episodes

A mood disorder characterized by

alternating periods of depression and
mania or hypomania.
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 • Imipramine • Phenelzine • Trazodone
• Fluoxetine • Duloxetine
• Desipramine • Tranylcypromine • Nefazodone
• Fluoxamine • Bupropion
• Clomipramine • Moclobemide
• Paroxetine • Mianserin
• Amitriptyline
• Citalopram • Reboxetine
• Nortriptyline
• Escitalopram
• Doxepin 22
Selective Serotonin Reuptake Inhibitors (SSRIs)

Definition: Selective serotonin reuptake

inhibitors (SSRIs) are a class of medications
primarily used to treat depression and various
anxiety disorders. They work by increasing the
level of serotonin, a neurotransmitter, in the
brain.
Mechanism of Action (MOA):
SSRIs block the reuptake (reabsorption) of
serotonin into neurons. This increases the
availability of serotonin in the synaptic cleft
(the space between neurons), enhancing
neurotransmission and improving mood.
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 ADVERSE EFFECTS
USES: •Gastrointestinal Symptoms
•Central Nervous System Effects
•Sexual Dysfunction: Decreased libido,
•Major Depressive Disorder (MDD): Primary
delayed ejaculation
treatment for clinical depression. •Weight Changes: Some patients may
•Anxiety Disorders: Including generalized experience weight gain or loss.
anxiety disorder (GAD), panic disorder, social •Hyponatremia: low sodium levels in the
anxiety disorder, and obsessive-compulsive blood.
•Serotonin Syndrome: A potentially life-
disorder (OCD).
threatening condition caused by too much
•Post-Traumatic Stress Disorder (PTSD): serotonin, leading to symptoms like
Helps reduce symptoms of PTSD. agitation, confusion, rapid heart rate,
•Premenstrual Dysphoric Disorder (PMDD): dilated pupils, loss of muscle coordination,
Reduces severe premenstrual symptoms. or muscle rigidity.
•Withdrawal Symptoms
•Eating Disorders: Sometimes used for
•Emotional Blunting
conditions like bulimia nervosa. •Increased Risk of Bleeding

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 Tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a class of medications used primarily to treat depression
and certain anxiety disorders. They are among the older classes of antidepressants and are
named for their chemical structure, which includes three rings of atoms.

Mechanism of Action (MOA):

TCAs work by inhibiting the reuptake of
neurotransmitters serotonin and
norepinephrine, increasing their levels in the
brain. This enhances neurotransmission and
improves mood. TCAs also affect other
neurotransmitter systems, including those for
acetylcholine and histamine, which contribute
to their side effects.
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 ADVERSE EFFECTS
•Anticholinergic Effects: Dry mouth, blurred vision,
Uses of Tricyclic antidepressants constipation, urinary retention, and increased heart rate.
•Cardiovascular Effects: Orthostatic hypotension,
tachycardia, and potential for arrhythmias.
•Central Nervous System Effects: Sedation, drowsiness,
dizziness, confusion, and cognitive impairment,
especially in older adults.
•Major Depressive Disorder (MDD): Primary use for the •Weight Gain: Can lead to significant weight gain.
treatment of depression. •Sexual Dysfunction: Decreased libido, erectile
•Anxiety Disorders: Used for conditions such as dysfunction, and anorgasmia.
generalized anxiety disorder (GAD) and panic disorder. •Gastrointestinal Effects: Nausea and vomiting.
•Chronic Pain: Effective in treating neuropathic pain, •Seizures: Lowered seizure threshold, increasing the risk
fibromyalgia, and other chronic pain conditions. of seizures.
•Suicidality: Like other antidepressants, TCAs may
•Obsessive-Compulsive Disorder (OCD): Clomipramine, a
increase the risk of suicidal thoughts and behaviors
TCA, is particularly effective for OCD. •Photosensitivity: Increased sensitivity to sunlight,
•Insomnia: Due to their sedative properties, TCAs can be leading to skin reactions.
used to treat sleep disturbances. •Withdrawal Symptoms: Abrupt discontinuation can lead
•Enuresis (Bedwetting): Used in children for nocturnal to withdrawal symptoms such as nausea, headache, and
enuresis due to their anticholinergic effects. malaise.

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 MAO Inhibitors MAO-A5-HT MECLOBEMIDE

Monoamine Oxidase is an enzyme which metabolizes NA, Inhibits MAO

5-HT and DA. Drugs which inhibits this enzyme increases
the concentration of monoamines in neuronal levels. SEROTONIN NOT
Mechanism of Action (MOA): Monoamine oxidase METABOLIZED
inhibitors (MAOIs) are a class of antidepressant drugs that
work by inhibiting the activity of the enzyme monoamine Increased serotonin level in
synapse
oxidase. This enzyme is involved in the breakdown of
monoamine neurotransmitters such as serotonin,
norepinephrine, and dopamine. By inhibiting monoamine Antidepressant effect
oxidase, MAOIs increase the levels of these
neurotransmitters in the brain, which can help alleviate
symptoms of depression and certain anxiety disorders.
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 CHEESE REACTION-Tyramine containing food-
cheese, beer, wine, yeast, buttermilk, fish-
Uses of Monoamine Oxidase Inhibitors (MAOIs) Tyramine metabolized by MAO.
MAO inhibits-tyramine escapes metabolism-
Clinical Uses: displaces NA-hypertension
1.Major Depressive Disorder (MDD):
Particularly effective for atypical depression
ADVERSE EFFECTS
(characterized by mood reactivity, increased
appetite, increased sleep, and sensitivity to
rejection). Adverse Effects of Monoamine Oxidase Inhibitors
2.Anxiety Disorders: 1.Orthostatic Hypotension: Drop in blood
Effective for panic disorder and social anxiety pressure upon standing, leading to dizziness or
disorder. fainting.
3.Parkinson's Disease: 2.Weight Gain: Increased appetite and
MAO-B inhibitors like selegiline and rasagiline subsequent weight gain.
are used to manage symptoms by increasing 3.Insomnia: Difficulty falling or staying asleep.
dopamine levels. 4.Sexual Dysfunction: Decreased libido, erectile
4.Treatment-Resistant Depression: dysfunction, and anorgasmia (difficulty achieving
Used when patients do not respond to other orgasm).
antidepressants like SSRIs, SNRIs, or TCAs. 5.Edema: Swelling due to fluid retention.

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 4 Mood
stabilizers
Mood stabilizers control the mood
swings that are seen in bipolar
mood disorders. They are also
called antimanic drugs.
Mood stabilizers include:
• Lithium
• Sodium valproate
• Carbamazepine
• Lamotrigine
• Gabapentin
Lithium has been used for several decades but several antiepileptics like
carbamazepine, valproic acid and gabapentin are now being tried.
MOOD STABILIZER-LITHIUM
• Lithium is a small ion and mimics the role of
sodium in excitable tissues.
• Given orally it is well-absorbed.
• It is filtered at the glomerulus but reabsorbed
like sodium.
• Steady state concentration is reached in 5-6
days.
• Lithium is secreted in sweat, saliva and breast
milk. Since safety margin is narrow, plasma
lithium concentration needs to be monitored
(0.5-1 mEq/ Lit is the therapeutic plasma
concentration).
• 3-5 mEq/Lit can cause fatal toxicity.

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MOA OF MOOD STABILIZER-
•Lithium inhibits inositol monophosphatase,
LITHIUM an enzyme involved in the
phosphatidylinositol signaling pathway. This
inhibition reduces the availability of inositol,
Phosphatidylinositol-4,5-biphosphate Diacylglycerol a critical component for the synthesis of
phosphatidylinositol, leading to decreased
production of inositol triphosphate (IP3) and
diacylglycerol (DAG), which are important
secondary messengers in neurotransmission.
Inositol-1-4-5 triphosphate
•Result: This leads to reduced signal
transduction for neurotransmitters like
serotonin and norepinephrine, stabilizing
mood by dampening hyperactive
neurotransmission that may contribute to
mood swings.
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USES ADVERSE EFFECTS
1. Prophylaxis of bipolar mood disorder- 1. Lithium has low therapeutic index
episodes of mania and depression and and side effects are common.
their severity are reduced. 2. Nausea, vomiting, mild diarrhoea,
2. Acute mania-since the response to thirst and polyuria occur initially in
lithium is slow, neuroleptics are most patients.
preferred. 3. Weight gain can also occur.
3. Depression-lithium is tried along with 4. As the plasma concentration rises,
other antidepressants as an add-on hypothyroidism, CNS effects like
drug in the treatment of severe coarse tremors, drowsiness,
recurrent depression. giddiness, confusion, ataxia, blurred
4. Other uses-lithium is tried in recurrent vision and nystagmus are seen.
neuropsychiatric disorders, childhood 5. In severe overdosage, delirium,
mood disorders, hyperthyroidism and muscle twitching's, convulsions,
inappropriate ADH secretion syndrome. arrhythmias and renal failure
develop. 32
Thank you