INTRODUCTION TO

PSYCHOPHARMACOLOGY
 OBJECTIVES

• Identify major classes of somatic treatments for the

major DSM-IV-TR Diagnoses
• Describe basic mechanism of action of somatic
treatments
• Explain how mechanism of action related to major
side effect profiles
ANTIDEPRESSANTS
 TRICYCLIC ANTIDEPRESSANTS

• Block the re-uptake of three neurotransmitter

systems:
• Serotonin
• Norepinephrine
• Dopamine

• Utilized in:
• Major Depressive Disorder
• Dysthymia
• Generalized Anxiety Disorder
• Panic Disorder
• Obsessive-Compulsive Disorder
 TRICYCLIC ANTIDEPESSANTS

• Older “Dirtier” Medication:

• 3-4 weeks for onset (sometimes even 4-6 weeks)
• Can be lethal in overdose (cardiotoxic)
• Have side effect profiles:
• Anticholinergic: dry mouth, constipation, confusion, urinary
retention
• Histaminic blockade: sedation and weight gain
• Alpha-adrengergic blockade: orthostatic hypotention
• Serotinergic: sexual side effect
 MAOI

• Block Monoamine Oxidase in the wall of the gut,

CNS and platelets leading to build up of Dopamine
and Norepinephrine

• Utilized in:
• Major Depressive Disorder
• Atypical Depression
• Anxiety Disorders
 MAOI

• Inhibition of MAO in the gut leads to increased

Tyramine absorption. Hence, patients must avoid
Tyramine containing foods (fava beans, aged
meats and cheeses, wines, sauerkraut, etc…)
• Ingestion of Tyramine can lead to hypertensive crisis
• Require 3-4 weeks (sometimes 6-8 weeks)
• Fatal in overdose
• Cannot be combined with other serotinergic acting
drugs (Tricyclic’s, SSRI’s) due to risk of serotonin
syndrome.
• Overdose can be fatal
 SSRI

• Blockade of serotonin reuptake from the synapse

• Utilized in:
• Major Depression
• Dysthymia
• OCD
• Panic Disorder
• PTSD
• Social Phobia
• Bulimia Nervosa
• Depressed phase of Bipolar (only with a mood stabilizer)
 SSRI

• Take 2-4 weeks for onset

• Fewer side effects than older medications –
“Cleaner” and more easily tolerated
• First line agents in pregnancy (although Class C)

• Major side effects:

• Gastrointestinal (first few days)
• Sexual Side Effects
• Black Box Warning: Increased Suicidality in Adolescents
• Treatment emergent mania in bipolar disorder
• Discontinuation Syndrome
 SNRI

• Blocks Re-uptake of Serotonin and Norepinephrine

• Careful balance between two neurotransmitter
systems
• Utilized in Depression, Anxiety and Pain Syndromes
• “Cleaner”/More Easily Tolerated
• Major Side Effects:
• Blood Pressure
• Discontinuation Syndrome
 MISCELLANEOUS

• Wellbutrin (Buproprion)
• Inhibition of Norepinephrine Re-uptake
• No sexual side effects
• Also marketed as Zyban for smoking cessation
• Contraindicated in eating disorders due to lowering seizure
threshold
• Main side effect is anxiety

• Remeron (Mirtazapine)
• Alpha-2 Antagonist (net effect -> increased norepinephrine)
• May cause sedation or increased weight gain
• Often used in the elderly
SEDATIVES/ANXIOLYTICS
 BENZODIAZAPINES

• Use is determined by ½ life:

• Long (Diazepam, Chlorediazepoxide)
• Medium (Alprazolam)
• Short (Lorazepam)

• Utilized for panic and insomnia

• Potentiation of GABA receptors by binding to
special binding site
• Long-term use may lead to tolerance, withdrawal
and physiologic dependence
• Side effects are sedation and amnesia
 OTHERS

• Beta-Blockers –
• Utilized for performance anxiety
• Centrally acting/lipophilic  propranolol
ANTIPSYCHOTICS
 TYPICAL ANTIPSYCHOTICS

• High Potency (Haldol)

• Primary action is blocking D2 receptors (antagonist)
• High affinity for D2 = lower dose
• Good control of positive symptoms
• Major Side Effects:
• EPS -dystonic reactions, prolactin, akasthesia, parkinsonism
• Neuroleptic Malignant Syndrome –
• Mid/Low Potency (Thorazine)
• Lower affinity for D2 = higher dose
• Less EPS
• More anticholinergic, alpha-adreinergic, and histiminic side
effects
 DOPAMINE HYPOTHESIS OF
SCHIZOPHRENIA
Mesocortical pathway
Hypoactivity: Nigrostriatal pathway
negative, cognitive, (part of EP system)
and mood symptoms

Mesolimbic pathway
Hyperactivity:
positive symptoms
Tuberoinfundibular pathway
(hallucinations,
(inhibits prolactin release [D2])
delusions)
 Clinical profile: Dopamine (D2)
blockade

EFFICACY: (+) SSX

Mesolimbic D2

MesocorticalD2 INEFFICACY: (-) SSX,

cognition, mood

SIDE EFFECTS: EPS

Nigrostriatal D2

D2 SIDE EFFECTS: HPL

Tuberoinfundibular
 SCHIZOPHRENIA (TREATMENT)

HIGH MEDIUM LOW

Fluphenazine (D) Perphenazine Thioridazine

Prochlorperazine Chlorpromazine
Trifluoperazine Loxapine
Thiothixine Acetophenazine
Haloperidol (D) Triflupromazine
Chlorprothixine
Mesoridazine

EPS, HPL EPS, HPL

Anti-H1: Sedation, wt gain Anti-H1

Anti-α-1: Orthostasis, reflex tachycardia Anti-α-1
Anti-M1: Blurry vision, dry mouth, Anti-M1
constipation, urinary retention, tachycardia,
memory problems or delirium in susceptible Seizure, arrythmias, retinitis,
patients skin discoloration, photosens
 EPS

• Dystonia – acute, involuntary muscle spasms often seen

in ocular muscles and neck

• Parkinsonism – tremor, cogwheel rigidity, masked facies,

and shuffling gait

• Akasthesia – a subjective sense of restlessness.

• Tardive Dyskinesia – long-term involuntary jerking of face,

neck, trunk or extremities. May be permanent.
http://www.youtube.com/watch?v=R0EbgpyztCA
ATYPICAL (SECOND GENERATION)

• Utilized in:
• Acute Schizophrenia
• Maintenance of Schizophrenia
• Acute Mania
• Maintenance of Bipolar
• Treatment of Bipolar Depression
• Mechanism of Action: Blockade of D2 and 5HT-2A.
Serotonin modulate dopamine, particularly in the
nigrostriatal pathways. Hence, more Dopamine
blockade in the mesolimbic as opposed to
nigrostriatal pathways.
 A. B.

5HT DA DA
release

C. D.

+/- DA
5HT DA
release
 ATYPICALS

• Often first line

• Efficacy on positive and negative symptoms
• NMS and EPS unlikely
• Side Effects are based on receptor profile
• Prolongation of QTc (Cardiovascular)
• Metabolic Syndrome
• Weight Gain
• Glucose Intolerance
• Increased Lipids and Triglycerides
MOOD STABILIZERS
 LITHIUM

• Indicated for acute mania and maintenance

bipolar
• Specific evidence to support use in preventing
suicide
• Blocks inositol-1-phosphatase
• Narrow therapeutic range: dangerous in overdose
• Side Effects:
• Tremor
• Renal Impairment
• Thyroid Dysfunction
• Cardiovascular
 ANTICONVULSANTS

• Major Agents: Carbamazepine, Valproic Acid and

Lamotrigene
• May prevent kindling
• Each agent has side effects that are outside scope
of this lecture
 SUMMARY
Disorder Treatment

Depression SSRI, SNRI, Buproprion, Mirtazepine

Atypical Depression
Anxiety Disorders
OCD
PTSD
Performance Anxiety
Psychosis
Acute Mania
Bipolar Maintenance
Bipolar Depression
Rapid Cyclling/Mixed Episodes
MAOI
Short-Term: Benzodiazepine
Long-Term: SSRI, SNRI
High Dose SSRI, Tricyclics
SSRI
Beta-Blocker
Atypical Antipsychotic
Atypical Antipsychotic, Lithium,
Carbamazepine
Atypical Antipsychotics, Lithium
Carbamazepine
Lamotrigine, Some Atypicals
Valproic Acid