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Psychotic Medications
Danesh A. Alam, M.D.
Fellow, Psychopharmacology and Research
Psychiatric Clinical Research Center
University of Illinois at Chicago
Rauwolfia Serpentina:
The First Herbal Antipsychotic
The first antipsychotic, Rauwolfia Serpentina, was
prescribed by physicians in ancient India over two
millennia ago.
The ancient Ayurvedic pharmacopoeia describes the use
of R. Serpentina in the treatment of insanity
(oonmaad in Sanskrit). onmaad is a description of
psychosis by the Ayurvedic physician Chakra (circa
1000 BC) as an abnormal condition of the mind,
wisdom, perception, knowledge, memory, character,
creativity, conduct, and behavior.
Rauwolfia Serpentina:
The First Herbal Antipsychotic
In 1931, Sen and Bose described the tranquilizing and
antihypertensive effects of R. Serpentina root extracts.
(Rauwolfia Serpentina: a new Indian drug for insanity and
high BP. Indian Medical World 1931:11:194-201).
In 1952, reserpine was isolated from Rauwolfia extracts.
Arvid Carlsson (Sweden) discovered the central nervous
system neurotransmitter properties of dopamine while
studying the mechanism of action of reserpine. Reserpine
works by depleting cells of dopamine, thus, reducing brain
dopaminergic activity.
Antipsychotics
Common Indications
Schizophrenia
Schizoaffective
disorder
Mood Disorder with
psychosis
Dementia with
psychosis
Delirium
Delusional disorder
Psychosis secondary to
a non-psychiatric
medical disorder
Developmental
disability with
psychosis and/or
aggression
Tourettes disorder,
Huntingdons
chorea, intractable
hiccups
Acute Mania
Augmentation in
Major Depression
and Bipolar disorder
Dopamine Receptors
Plethora of DA receptors exist
5 pharmacological subtypes:
D1, D2, D3, D4 and D5
D2 Receptor: Most extensively studied
Stimulated by agonists for treatment of Parkinson's
Blocked by antagonists for treatment of Schizophrenia
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
2nd Generation/Novel/Atypical?
Profile
Diminished extrapyramidal side effects (EPS)
Minimized risk for tardive dyskinesia (TD)
No hyperprolactinemia
Beneficial for treatment of refractory patients
Improved negative symptoms
Improved cognitive/mood symptoms
Disadvantages
Agranulocytosis
Negative symptoms
Seizures
Weight gain
No prolactin increase
Orthostasis
Tachycardia
Sedation
Sialorrhea
Constipation
Refractory Psychosis
Change anti-psychotic after adequate dosage
trial
Consider noncompliance and depot injections
Antipsychotic combinations
e.g., addition of neuroleptic
Adjunctive medications
Antipsychotic Combinations I
Proposed Rationale:
Extensive unpublished clinical experience? (difficult
to examine without bias)
Differences in pharmacological action between
typicals and atypicals? (poor understanding of
required neurochemical action)
Antipsychotic Combinations II
Temporary Situations:
Lead-In combinations - typicals supposedly
having more rapid action during acute
emergency)
Top-Up combinations - addition of typical to
overcome acute exacerbation
Adjunctive Treatment
Anticholinergics
Dose-related EPS
Primary vs. secondary negative symptoms
Neuroleptic malignant syndrome
Tardive dyskinesia (other tardive syndromes)
NEUROLEPTICS
Minimum
RISPERIDONE
OLANZAPINE
(DOSE-RELATED
CLOZAPINE
ZIPRASIDONE
QUETIAPINE
Management
Stop agent
Reverse isolation; supportive measures
GCSF (cytokines, filgastrim)
Rechallenging strategies
Hypotension
Tachycardia
Arrhythmogenic potential possible with all
antipsychotics
QTC interval
QTC prolongation
QTC dispersion
Torsade de Pointes
Lactation/breast engorgement
Gynecomastia
Sexual dysfunction (decrease in sexual interest reversed
by bromocriptine)?
Anxiety and mood disturbance?
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Diabetes
Hypertension
Serum cholesterol
Trivia
Antipsychotic that cause less weight gain: molindone
& ziprasidone
droperidol- only approved for IV use in anaesthesia
Pimozide approved for use in Tourettes only
Clozapine- reduces suicide in schizophrenia
All antipsychotics lower the seizure threshold, 2nd
generation <1%
Other meds that cause ac. Dystonia, akathesia,
parkinsonian sideeffects and NMS- prochorperazine
(compazine), metoclopramide, promethazine
(Phenergan).