DRUGS FOR

PSYCHIATRIC DISORDERS

ANTIPSYCHOTIC DRUGS
ANTI-ANXIETY DRUGS
ANTIDEPRESSANT DRUGS
LITHIUM
 ANTIPSYCHOTC DRUGS
The antipsychotic drugs also known as neuroleptic drugs are useful
for the treatment of schizophrenia, agitated states & other
psychosis.
SCHIZOPHRENIA: It is a psychosis with clear sensorium
but a marked thinking disturbance due to excessive
dopaminergic activity at the D2 receptors in the mesolimbic frontal
system. CLASSIFICATION (TYPICAL)
1. PHENOTHIZINE DERIVATIVES: Chlorpromazine, Thioridazine,
Trifluoperazine, Perphenazine.
2. THIOXANTHINE DERIVATIVES: Thiothixine
3. BUTYROPHENONE DERIVATIVES: Haloperidol
4. MISCELLANEOUS: (ATYPICAL) Pimozide, Molindone, Clozapine,
Ziprasidone, Aripiprazole, Risperidone.
MECHANISM OF ACTION: Chlorpromazine blocks the
D2 receptors in the mesolimbic mesofrontal dopaminer-
-gic fibers to show antipsychotic effects. Receptors like
alpha, muscarinic, histaminic(H1) and serotonin (5HT2)
are also blocked to show non-antipsychotic effects.
PHARMACOLOGICAL EFFECTS:
(a) PSYCHOLOGICAL EFFECTS: Psychotic persons
show improvement in their performance. The non-
-psychotic persons suffer from sleepiness, restless-
-ness, impaired performance & muscarinic effects.
(b) NEUROPHYSIOLOGIC EFFECTS: Slowing of
electroencephalographic frequencies and increase
in their synchronization.
ENDOCRINE EFFECTS: Amenorrhea, galactorrhea,
false +iv pregnancy tests & increased libido in women.
In men decreased libido and gyneacomastia.
CARDIOVASCULAR EFFECTS: Orthostatic hypotension,
high resting pulse rate & increased heart rate. Decrease
in the peripheral resistance, B.P. & stroke volume.
Prolongation of QT interval, abnormal configurations of
ST segment and T waves and arrhythmias.
PHARMACOKINETICS: Orally readily but incompletely
absorbed, undergo significant first-pass metabolism,
highly lipid soluble, 92-99% plasma protein bound,
longer duration of action. Mesoridazine is a more potent
metabolite of thioridazine. The metabolites of
chlorpromazine are excreted in the urine weeks after
the
ADVERSE REACTIONS:
(a) BEHAVIORAL: Akinesia, pseudodepression, toxic
confusional states with prominent anti-muscarinic
actions.
(b) NEUROLOGIC : Extrapyramidal reactions (Parkison-
-ism) seen as akathesia (uncontrolable restlessness)
and acute dystonic reactions (spastic retrocollis or
torticollis). Tardive dyskinesia (late occurring
syndrome of abnormal choreoathetoid movements)
which is due to decreased cholinergic activity
secondry to supersensitivity of dopamine receptors
in the caudate-putamen, less seen with atypical anti-
-psychotics. Seizures with chlorpromazine and
clozapine.
(c) AUTONOMIC: Antimuscarinic adverse effects.
Adrenoceptor-blocking effects like orthostatic hypo-
-tension and impaired ejaculation seen with
chlorpromazine & mesoridazine.
(d) METABOLIC & ENDOCRINE: Weight gain,
hyperglycemia, hyperprolactinemia in women leading
to amenorrhea-galactorrhea syndrome. In men loss of
libido, impotence and infertility.
(e) TOXIC or ALLERGIC REACTIONS: Agranulocytosis
(especially by clozapine), cholestatic jaundice and
skin eruptions.
(f) OCULAR: Chlorpromazine gets deposited in the lens
and cornea. Thioridazine gets deposited in the retina to
give “browning of vision.”
(g) CARDIAC: Thioridazine in high doses causes T-wave
abnormalities, ventricular arrhythmias, cardiac
conduction block and death. Ziprasidone causes QT
prolonation.
(h) PREGNANCY: These drugs carry the risk of
teratogenesis.
(i) NEUROLEPTIC MALIGNANT SYNDROME: It occurs due
to excessively rapid blockade of postsynaptic dopamine
receptors. Seen as muscle rigidity, high grade fever,
stress leucocytosis followed by a severe type of
extrapyramidal syndrome.
CLINICAL USES:
(A) PSYCHATRIC INDICATIONS:
1. Schizophrenia
2. Schizoaffective disorders
3. Manic episode (in bipolar affective disorder)
4. Tourette”s syndrome.
5. To control psychosis and agitation in depression.
6. Senile dementia of Alzheimer type.
(II) NON-PSYCHIATRIC INDICATIONS:
1. Antiemetic
2. Antipruritic
3. Preoperative sedatives
4. Neuroleptanesthesia
 ANTIANXIETY DRUGS
The antianxiety drugs also known as anxiolytics are
basically sedative-hypnotics. They are used for the
relief of anxiety. In low doses they produce sedation
and in high doses they will produce sleep.
CLASSIFICATION
(a) BENZODIAZEPINES: Diazepam, Chlordiazepxide,
Flurazepam, Oxazepam, Lorazepam, Triazolam
(b) BARBITURATES: Pentobarbital, Secobarbital,
Phenobarbital,
(c) MISCELLANEOUS: Buspirone, Zolpidem, Zaleplon
Chloral hydrate
MECHANISM: The benzodiazepines enhance GABA-ergic
inhibition at the GABA receptor. The barbiturates
increase the duration of opening of chloride channel
and inhibit the stimulation of glutamate receptor.
ACTIONS: The anxiolytics produce relief of anxiety,
sedation, hypnosis, anesthesia, anticonvulsant effects,
muscle relaxation, respiratory depression in pulmonary
disease, cardiovascular depression, psychologic and
phsyiologic dependence.
TOXICITY: Impaired judgement, diminished motor skills,
delerium, agression, violence, behavioral disinhibition,
hypersensitivity and teratogenecity.
NEWER DRUGS:
1. Buspirone has selective anxiolytic effects without
sedation or euphoria. It acts as a partial agonist at
brain 5HT1A receptors. It does not interact with
 GABA-ergic system and does not show anticonvulsant,
hypnotic or muscle relaxant properties. It has also
affinity for dopamine D2 receptors. It does not show
rebound anxiety, has minimal abuse liability. Adverse
effects are tachycardia, palpitations, nervousness, GIT
distress and parasthesias.
2. Zolpidem binds to BDZ-subtype of receptor and
facilitates GABA-mediated neuronal inhibition. Actions
are antagonized by flumazenil. It can suppress REM
sleep and causes rebound insomnia after abrupt
discontinuation of the drug. Respiratory depression
occurs when taken with alcohol.
3. Zaleplon facilitates inhibitory actions of GABA,
produces rapid onset and short duration of sleep.
Amnesia and next day impairment of psychomotor
performance occurs.
4. Venlafaxine and paroxetine (antidepressants) are drugs

of first choice in generalized anxiety disorders.

 ANTIDEPRESSANT DRUGS
Depression is a common psychiatric disorder classified
into three groups:-
• Reactive or secondary depression occuring in
response to real stimuli e.g., grief, illness.
• Endogenous (Major) depression, a genetically
determined biochemical disorder.
(c) Manic-depressive (Bipolar-affective) disorder with
alternate phases of mania and depression.
PATHOPHYSIOLOGY: There is depletion of serotonin
or norepinephrine (or both) in the vesicles of
pre-synaptic nerve endings of the CNS.
 CLASSIFICATION
(a) TRICYCLIC ANTIDEPRESSANTS (TCAs): Imipramine,
Amytryptyline, Doxepin, Desipramine.
(b) HETEROCYCLICS: (second & third generation drugs)
Amoxapine, Maprotiline, Trazodone, Bupropion,
Venlafaxine, Mirtazipine.
(c) SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS
(SSRIs): Fluoxetine, Paroxetine, Sertraline,Citalopram.
(d) MONOAMINE OXIDASE INHIBITORS (MAOIs):
Phenalzine, Isocarboxazid, Tranylcypromine.
PHARMACOKINETICS: The effects of tranylcypromine
persist for seven days and those of phenelzine last
for 2-3 weeks after discontinuation of the drug.
MECHANISM: Tricyclics block the amine (norepinephrine or
serotonin) reuptake pumps, which terminate amine
neurotransmission. This permits longer availability of
neurotransmitters at the receptor site.
The MAOIs block the metabolism of the
amine neurotransmitters which permits more amines to
accumulate in presynaptic stores and more to be released.
The heterocyclics (second generation) have
mechanism like tricyclics & MAOIs. They also antagonise
subtypes of serotonin receptors (5HT2A or 5HT2C).
Bupropion alters the output of norepinephrine and
occupy 25% of dopamine reuptake pumps. Mirtazapine
(third generation) also antagonises alpha-receptors.
The SSRIs inhibit 80% of serotonin
reuptake pumps and permit accumulation of serotonin in
the synaptic cleft.
 Moreover there is decrease in the intracellular cAMP,
down-regulation of beta-receptors and phosphorylation of
regulatory elements.
EFFECTS OF SPECIFIC ANTIDEPRESSANTS:
The first generation antidepressants (tricyclics) have
varying degrees of selectivity for the reuptake pumps for
norepinephrine and serotonin. They have also autonomic
effects.
The second generation drugs, like amoxipine shows both
antipsychotic and antidepressant effects, but dopamine
receptor blockade causes akathesia, parkinsonism etc.
The third generation drugs, like venlafaxine is a potent
inhibitor of serotonin pumps. Mirtazapine is a potent
anti-histaminic with greater sedating effects and does not
decrease libido or sexual function.
The SSRIs cause decrease in libido and sexual function.
They cause serotonin syndrome when used in combination
with MAOIs due to marked increase of serotonin in the
synapses.
The MAOIs which block irreversibly both A & B forms of
MAOs are subject to very high risk of hypertensive crisis
if tyramine containing foods are taken (because of the loss
of first-pass hepatic metabolism of tyramine).
Moclobemide is a short acting MAO inhibitor is free of the
above effects. Selegeline is a selective MAO-B inhibitor so
metabolism of dopamine is inhibited and its amount
increases, which makes it useful for parkinsonism.
ADVERSE EFFECTS
TRICYCLICS: Sedation, tremor, insomnia, blurred vision,
constipation, urinary hesitancy, confusion, hypotension,
 conduction defects, arrhythmias, aggravation of psychosis,
withdrawl syndrome, seizures, weight gain, sexual
disturbances.
MAOIs: Sleep disturbances, weight gain, postural
hypotension, sexual disturbances ( by phenelzine)
AMOXAPINE: Similar to tricyclics plus some of
antipsychotics.
MIRTAZAPINE: Somnolence, increased appetite, weight gain
dizziness.
TRAZODONE , NEFAZADONE: Drowsiness, dizziness,
insomnia, nausea, agitation.
VENLAFAXINE: Nausea, somnolence, sweating, dizziness,
sexual disturbances, hypertension, anxiety.
BUPROPION: Dizziness, dry mouth, sweating, tremor,
agravation of psychosis, seizures (high doses).
FLUOXETINE (other SSRIs): GIT symptoms, decreased libido,
sexual dysfunction, anxiety, insomnia, tremor.
CLINICAL USES
1. Depression
2. Panic disorder
3. Obcessive-compulsive disorder
4. Enuresis
5. Chronic pain
6. Bulimia (eating disorder)
7. Attention Deficit Hyperkinetic Disorder (ADHD)
8. Social disorder
9. Generalized Anxiety Disorder
 LITHIUM
Lithium carbonate is known as antimanic drug, also known
as “mood stabilizing” agent primarily used for bipolar
affective (manic-depressive) disorders. Carbamazepine is
also useful for manic-depressive patients. Valproate is
useful
for mania and is a mood stabilizer. The atypical antipsycho-
-tics are approved as antimanic agents and mood stbilizers.
BIPOLAR AFFECTIVE DISORDER: