PHARMACOTHERAPY IN PSCHIATRY

 DEPRESSION
 SCHIZOPHRENIA
 BIPOLAR DISORDERS

SCHIZOPHRENIA
ETHIOLOGY
Exact etiology unknown
Genetic predisposition
Intrauterine, birth or postnatal complications
Viral CNS infections
Environmental stressors (biochemical or social)
No evidence of association with poor parenting

POSITIVE SYMPTOMS NEGATIVE SYMPTOMS

Hallucination Social withdrawal

Delusions Emotional withdrawal

Disordered thinking Lack of motivation

Disorder speech Poverty of speech

Combativeness Blunted affect

Agitation Poor insight

Paranoia Poor judgement

Poor self-care
ANTIPSYCHOTICS
 Typical/conventional antipsychotics
 Atypical antipsychotics

TYPICAL/ CONVENTIONAL ANTIPSYCHOTICS

 Chlorphomazine (Largactic)
 Haloperidol (Serenace, Haldol)
 Flupenthixol (Fluanxol)
 Pericyazine (Neulactil)
 Pimozide (Orap, Orap Forte)
 Sulpiride (Dogmatil)
 Thioridazine (Melleril)
 Trifluoperazine (Stelazine)
 Thiothixene (Navane)

also known as
 “dopamine receptor antagonist”
-pharmacologic activity at blocking central dopamine receptors (esp. D2
receptors)
 “neuroleptics”
-due to tendency to cause neurologic adverse effects
 “major tranquilizers”
 -inappropriate as these agents (esp. high potency) can improve psychosis
without sedating or making patients tranquil

Mechanism of action
 Blocks receptors for dopamine, acetylcholine, histamine and noreepinephrine
 Current theory suggests Dopamine2 (D2) receptors suppresses psychotic
symptoms
 All typical antipsychotics block D2 receptors
 Close correlation between clinical potency and potency as D2 receptor
antagonists

Adverse effects
 Extrapyramidal symptoms (EPS)
 Early reactions- can be managed with ddrugs
 Acute dystonia
 Parkinsonism
 Akathsiia
 Late reaction - drug treatment unsatisfactory
 Tardive dyskinesia
 Early reactions occur less frequently with low potency drugs
 Risk od TD is equal with all agents

ATYPICAL ANTIPSYCHOTICS
 Refers to new agents
 Also known as
 “Serotonin-dopamine antagonists”
 Postsynaptic effects at 5-HT2A and D2 receptors

 Amisulpiride (Solian)  Quetiapine (Seroquel)

 Ziprasidone (Zeldox)  Clozapine (Clozaril)
 Risperidone (Risperdal)  Aripiprazole (Abilify)
 Olanzapine (Zyprexa)

Clozapine
 Contraindication
 History of clozapine-induced agranulocytosis
 Bone marrow suppression
 On myelosuppressive drugs
 Caution
 Seizure disorders
 Diabetes

NON-ANTIPSYCHOTIC AGENTS
Benzodiazepines
 Useful in some studies for anxiety, agitation, global impairment and psychosis
 Schizophrenic patients are prone to BZD abuse
 Limit use shorts trials (2-4 weeks) for management of severe agitation and
anxiety
Lithium
 Limited role in schhizophrenia monotherapy
 Improve psychosis, depression, excitement and irritability when used with
antipsychotic in some studies.

DEPRESSION
 Depressed mood and/or decrease in interest in things that used to give pleasure
 Sadness severe enough or persistent enough to interfere with funtion
 DSM-IV
 Major depressive disorder / major depression
 Dysthymia
  depressive for most of the day, more days than not
 Depressive disorder not otherwise specified
 Depressive disorder due to a general physical condition
 Substance-induced depressive disorder

Epidemiology
 Life prevalence 3-17%
 Onset in late 20s
 Highest in
 25-44 years
 Elderly in community
 Female vs Male = 2:1
 Female 10-20% lifetime risk
 Male 5-12% lifetime risk
Signs and symptoms
 Depressed mood  Concentration loss
 Sleep (insomia or hypersomnia)  Appetite (loss or gain)
 Loss of interest (including libido)  Psychomotor (agitation or
retardation)
 Guilt
 Suicide (ideation)
 Energy loss

Pathophysiology
 Exact course unknown
 Change in receptor-neurotransmitter relationship in limbic system
 Serotonin, norepinephrine, somtimes dopamine
 Increased pump uptake of neurotransmitters
 Reabsorption into neuron
  Destroyed by monoamine oxidase in mitochondria
 Lack of neurotransmitters

Antidepressants
 Tricyclic and related antidepressants (TCA)
e.g. amitriptyline, imipramine, doxepin, mianserin, trazodone
 Monoamine-oxidase inhibitors (MAOI)
e.g. moclobemide, phenelzine, isocarboxazid, tranylcypromine
 Selective serotonin reuptake inhibitors (SSRI)
e.g. fluoxetine, paraxetine, sertraline, citalopram
 Other antidepressants
e. mirtazapine, venlafaxine, duloxetine, flupentixol

Tricyclic and related antidepressants (TCA)

 Amitriptyline (Saroten)
 Clomipramine (Anafranil)
 Dothiepin (a.k.a. Dosulepin,
Prothiaden)
 Imipramine (Tofranil)
 Mianserin (Tolvon)
 Nortriptyline (Nortrilen)
 Trazodone (Trittico)
 Trimipramine (Surmontil)

Mechanism of action
 Blocks neuronal uptake or norepinephrine and serotonin
 Initial response develops in 1-3 weeks
 Maximal response develops in 1-2 months
 Older tricyclic
 Marked anticholinergic adversse effects
 Risk of carditoxicity
 Tricyclic-related drugs (e.g. trazodone)
 Fewer anticholinergic adverse effects
  Sedation, dizziness, priapism (persistent penile erection accompanied by
pain and tenderness)

Properties
 Inexpensive, generic
 Some with off-label use, e.g.
 Neuropathy with amitriptyline
 Refractory skin diseases with doxepin
 Very dangerous in overdose
 Life threatening
 Lethal dose only 8 times average daily dose
 Acutely depressed patients should not be given more than 1-week TCA
supply at one time

Monoamine-oxidase inhibitors (MAOI)

Properties
 Useful in atypical depression (somnolence and weight gain), refractory disorder
and certain types of anxiety disorders
 Less prescribed than tricyclics, SSRIs and other antidepressants
 Danger of dietary and drug interactions

Adverse effects
 Hypertensive crisis
 Severe occipital headache, photophobia, palpitation, sharply increased in BP
due to addictive effect between MAOI and adrenergic stimulants
 Tyramine-rich food e.g. cheese, wine, smoked/aged picked meat or fish,
alcohol
 Amphetamine
 Pseudoephedrine