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The psychoses are among the most severe psychiatric disorders. People with this disorder suffer
from a

marked impairment of behaviour.


There are at least two subdivisions of psychosis

: (a) organic, and (b) functional (of unknown cause)


Organic psychoses are associated with

causes that are understood and definable e.g. toxic,
metabolic or neuropathological changes. T


Functional (of unknown cause) psychoses are characterized by

retention of orientation and
memory in the presence of severely disordered thought or reasoning, emotion and behaviour.
The functional psychoses include schizophrenia


Affective disorders are characterized primarily by a

change in emotion or mood


Affective disorders consist mainly of a single
disorder of mood - either mania or

severe depression


Mania is characterized by elation,
hyperactivity, and uncontrollable thought and speech. An individual suffering from

m depression
has feelings of intense sadness and self-disapproval, and physical and mental slowing.


An individual suffering from manic-depressive disorder exhibits

alternating periods of mania
and depression.


In contrast to the psychoses, individuals suffering from neuroses retain the ability to

comprehend reality


Neuroses - . The symptoms may involve mood
changes such as anxiety, panic or restlessness, and a feeling of being ill at ease. Individuals may
exhibit limited

abnormalities of thought such as obsessions or irrational fears or of behaviour
such as rituals or compulsions.


Symptoms of
schizophrenia are classified as

positive and negative.


The positive symptoms include delusions
and hallucinations, bizarre behaviour, lack of logic and incoherence while

apathy, social
withdrawal and loss of motivation are among the symptoms referred to as negative symptoms.


The theory of schizophrenia – the dopamine hypothesis is the most fully developed theory of
schizophrenia, but recent evidence indicates

that other neurotransmitters such as serotonin,
gamma-aminobutyric acid, and glutamic acid may be involved in schizophrenia.


schizophrenia =

excessive dopaminergic activity


Two other transmitters have also been postulated to play a role in schizophrenia

serotonin and glutamate.


Most of the “typical” antipsychotic drugs are

potent blockers of postsynaptic dopamine
receptors in the CNS


Drugs that increase dopaminergic activity such as levodopa (a precursor of dopamine),
amphetamines (releasers of dopamine), or apomorphine (a direct dopamine receptor
agonist) either

aggravate schizophrenia or induce it in some individuals.


Using a technique known as positron emission tomography (PET), dopamine receptor
density has been shown to be

higher in schizophrenic than in non-schizophrenic persons.


Antipsychotic action can be explained by antagonism of dopamine receptors in the

mesolimbic and mesofrontal systems of the brain (meso = middle)


Extrapyramidal movement disorders: Antagonism of dopamine receptors in the

nigrostriatal system.


Extrapyramidal movement disorders: Endocrine effects: Dopamine in the hypothalamus exerts a tonic inhibitory effect on prolactin
release from

m the pituitary gland


Blockade of histamine receptors:
Adverse effects:

Sedation, drowsiness, and weight gain


Blockade of α-adrenoceptors:
Adverse effects:

Postural hypotension (hypotension when assuming an erect position),
dizziness, reflex tachycardia


Clozapine is a very useful addition to our therapeutic armamentarium of antipsychotic drugs
because it relieves both the positive and negative symptoms of schizophrenia. Since patients
have fewer

extrapyramidal side effects when taking clozapine, compliance is better with
clozapine than with older antipsychotics


Clozapine can cause

granulocytopenia (a decrease in
the number of white blood cells)


Lithium carbonate is a mood-stabilizing agent which is used to prevent mood swings in patients

manic-depressive disorder. It is also used to treat mania.


The mechanism of action of lithium has not been resolved. Three possibilities are under

1. Effect on electrolytes and ion transport.
2. Effects on neurotransmitters and the release of neurotransmitters.
3. Effect on second messengers that mediate transmitter action.


Lithium is the drug of choice for long-term maintenance to prevent

both manic and depressive
episodes in patients with manic-depressive disorder


The safety and efficacy of lithium is enhanced by

monitoring serum lithium concentration


Antidepressant Agents-There are several
types of depression and depressions are classified as follows:

Reactive (secondary) depression. This is the most common type and accounts for over
60% of all depressions.

Major depression (endogenous). In major depression there are characteristic disturbances
of major body rhythms of sleep, hunger and appetite

Depression associated with manic-depressive disorder.


The major theory which has been proposed to explain major depression is known as the amine

Animal studies showed that reserpine inhibited reuptake and storage of serotonin and norepinephrine in the vesicles of presynaptic nerve endings. As a result, there was
a depletion of amine stores in these vesicles and amine-dependent neurotransmission would be
diminished. Since reserpine induced depression and depleted stores of amine neurotransmitters,
it was reasoned that depression might be associated with decreased functional amine dependent


The amine hypothesis does not explain all the effects of antidepressants in depression. The
neurotrophic hypothesis suggests that depression is associated with

reduced neurotrophic
(growth and inter-connectivity of neurons) support and that antidepressants stimulate
neurogenesis and synaptic connectivity in cortical areas.


Tricyclic antidepressants: Imipramine is a member of this class of antidepressants which share a

three-ring nucleus


Second-generation (atypical) antidepressants: Bupropion and amoxapine, introduced after
1980, are structurally unrelated to the tricyclic antidepressants and were introduced in an attempt

have available antidepressants with less adverse effects.


Selective serotonin reuptake inhibitors (SSRI’s):

The tricyclic antidepressants have anticholinergic
(muscarinic), antiadrenergic (alpha), and antihistaminic actions which do not contribute to their efficacy but do contribute to their toxicity. The SSRI’s, in contrast, have much less effect on the
autonomic nervous system and therefore have less toxicity.


Drugs that block Serotonin and norepinephrine uptake: Drugs such as venlafaxine block
transporters for both serotonin and norepinephrine and have an

advantage over the tricyclic
antidepressants due to their better safety profiles. (Less adverse effects).


Monoamine oxide (MAO) inhibitors: There are two monoamine oxidase (MAO) enzymes,
designated MAO-A and MAO-B. MAO-A is the enzyme primarily responsible for metabolism

norepinephrine, serotonin and tyramine.


MAO-B is more selective for dopamine metabolism.
Selective blockade of MAO-A is therefore

considered more selective for therapy of depression


Phenelzine and tranylcypromine are non-selective inhibitors of MAO-A and MAO-B. They
combine irreversibly with the enzymes and therefore have a

prolonged duration of action.


is a new

short-acting reversible inhibitor of MAO-A and 90% of the drug appears in urine within
12 hours of administration.


In the past, a tricyclic antidepressant such as imipramine has been considered as the drug of first
choice for treatment of



In recent years, an SSRI such as fluoxetine (Prozac) is often
used instead, especially for patients with

major depressive disorder anxiety disorder


SSRI’s: The SSRI’s cause nausea, headache, nervousness, and insomnia more commonly than

tricyclic antidepressants


MAO inhibitors: If MAO inhibitors are prescribed, patients must be warned that they interact
with dangerous consequences with many other drugs, both prescription and over-the-counter,
and with

tyramine-containing food