PSYCHOTHERAPEUTIC AGENTS
term control)
Psychoses – perceptual and behavioral disorders
Mental disorders are thought to be caused by some inherent
dysfunction within the brain that leads to abnormal though
processes and responses; disorders to some sort of chemical
imbalance in specific areas of the brain.
Diagnosis of a mental disorder is often based on
distinguishing characteristics described in the Diagnostic
and Statistical Manual of Mental Disorders, 4th edition, text
revision (DSM-IV-TR).
 Schizophrenia
o Most common type of psychosis
o Hallucinations, paranoia, delusions, speech
abnormalities, affective problems
 Mania
o With associated bipolar illness (manic-
depressive illness)
o Extremes of overactivity, excitement
o Bipolar – extremes of depression followed
by hyperactivity and excitement
o Biochemical imbalance followed by
overcompensation on the part of the
neurons and their inability to re-establish
stability
 Narcolepsy
o Daytime sleepiness and sudden periods of
loss of wakefulness
o Problems with stimulation of the brain by
the RAS or problems with response to that
stimulation
 Attention-deficit disorders
o Inability to concentrate on one activity for
longer than a few minutes and a state of
hyperkinesis
o Usually diagnosed in school-aged children
Antipsychotic/Neuroleptic Drugs
 essentially dopamine receptor blockers
 also called neuroleptic agents due to asscociated
neurological adverse effects
 formerly known as major tranquilizers
 classified as either typical or atypical
 typical antipsychotics are dopamine receptor
blockers
o can cause hypotension, anticholinergic,
antihistamine effects, extrapyramidal side
effects (EPS)
 Newer atypical antipsychotics block both dopamine
and serotonin receptors
 Indications
o Schizophrenia
o Hyperactivity, combative behavior,
agitation in the elderly, and several
behavioral problems in children (short-
 PK:
o Erratically absorbed from the GIT
o Stored in the tissues, released for up to 6
months after the drug is stopped
o Cross the placenta, enters breast milk
 CI
o CNS depression, circulatory collapse,
Parkinson’s disease, CAD, severe
hypotension, bone marrow suppression,
blood dyscrasias
o Mesoridazine, thioridazine, ziprasidone
can prolong QT interval
 Caution:
o Medical conditions that could be
exacerbated by anticholinergic effects:
glaucoma, peptic ulcer, urinary/intestinal
obstruction
o Seizures
o Thyrotoxicosis (severe neurosensitivity)
o Active alcoholism
o Pregnancy/lactation
o Myelography within last 24 hours or next
48 hours (severe neuron reaction to dye)
o Children < 12 yrs who have CNS infection
or chickenpox (not to be confused with
Reye’s syndrome)
 AE:
o Most common: sedation, weakness,
tremor, drowsiness, extrapyramidal effects
(pseudoparkinsonism, dystonia
(sustained muscle contractions
cause twisting and repetitive
movements or abnormal
postures), akathisia (or acathisia, is
a syndrome characterized by
unpleasant sensations of "inner"
restlessness that manifests itself
with an inability to sit still or
remain motionless), tardive
dyskinesia (epetitive, involuntary,
purposeless movements:
grimacing, tongue protrusion, lip
smacking, puckering and pursing
of the lips, and rapid eye
blinking), neuroleptic malignant
syndrome [muscle rigidity, fever,
autonomic instability and
cognitive changes such
as delirium, and is proven on a
raised creatine
phosphokinase (CPK)])
Possible anticholinergic effects include:
o Ataxia; loss of coordination
o Decreased mucus production in the nose
and throat; consequent dry, sore throat
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 o Xerostomia or dry mouth with possible
acceleration of caries
o Cessation of perspiration; consequent
decreased epidermal thermal dissipation
leading to warm, blotchy, or red skin
o Increased body temperature
o Pupil dilation (mydriasis); consequent
sensitivity to bright light (photophobia)
o Loss of accommodation (loss of focusing
ability, blurred vision — cycloplegia)
o Double vision (diplopia)
o Increased heart rate (tachycardia)
o Easily startled
o Urinary retention
o Diminished bowel movement, sometimes
ileus
o Increased intraocular pressure, dangerous
for people with narrow-angle glaucoma
o Shaking
 CV effects due to dopamine-blocking effects:
o hypotension
o Orthostatic hypotension
o Cardiac arrhythmias
o CHF
o Pulmonary edema
 Atypical antipsychotics - Risk for development of
diabetes mellitus
 not to be used to control behavioral symptoms of
dementia in older clients, risk for death
 phenothiazines turn urine pint to reddish-brown
 Drug-drug interaction:
o With beta blockers = inc effects of both
drugs
o With alcohol = CNS depression
o With anticholinergics = inc activity
o Chlorpromazine
 Management of manifestations of
psychotic disorders
 Relief of preop restlessness
 Adjunctive treatment of tetanus
 Acute intermittent porphyria
(rare autosomal dominant
metabolic
disorder affecting the
production of heme, the
oxygen-binding prosthetic
group of hemoglobin. It is
characterized by a
deficiency of
the enzyme porphobilinog
en deaminase. Symptoms
of AIP may
include abdominal
pain, constipation,
and muscle weakness.)
 Severe behavioral problems in
children
 Control of hiccups, NV
o Clozapine
 Management of severely ill
schizophrenics who are
unresponsive to standard drugs
 Reduction of risk of recurrent
suicidal behavior in patients with
schiz or schizoaffective disorder
ANTIMANIC DRUGS
 occurs in individuals with bipolar disorder, who
experience a period of depression followed by a
period of mania
 mania is thought to be an overstimulation of certain
neurons in the brain
 lithium salts (Lithane, Lithotabs)
o very toxic
o can cause severe CNS, renal and
pulmonary problems that may lead to
death
 Lamotrigine (Lamictal)
o Antiepileptic agent
o Long-term maintenance of bipolar disorder
o Decreases the occurrence of acute mood
episodes
 Atypical antipsychotics used for the short-term
management of acute manic episodes of bipolar
disorder in combination with lithium and valproate:
o Olanzapine (Zyprexa)
o Aripiprazole (Abilify)
o Ziprasidone (Geodon)
o Quetiapin (Seroquel) – also approved as as
adjunct or as monotherapy for th tx of
manic episodes associated with bipolar
disorder.
 Therapeutic action:
o Alters sodium transport in nerve and
muscle cells
o Inhibits the release of NE and dopamine,
but not serotonin
o Inc the intraneuronal stores of of NE and
dopamine slightly
o Dec intraneuronal content of second
messengers to selectively modulate the
responsiveness of hyperactive neurons that
might contribute to manic state.
 Indications
o Lithium is indicated for tx of manic
episodes of manic-depressive or bipolar
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 illness and for maintenance therapy to
prevent or diminish the frequency of and
intensity of future manic episodes.
o Being investifated for the improvement of
neutrophil counts in patients with cancer
chemotherapy-induced neutropenia and as
prophylaxis of cluster headaches and
migraine headaches
 PK:
o Kidney reabsorbs more lithium during
periods of sodium depletion or
dehydration leading to toxic levels
o Patients encouraged to maintain hydration
o Crosses placenta, enters breast milk – use
BC, D/C breast feeding
 CI:
o Allergy
o Pregnancy, lactation
o Significant renal, cardiac disease
o History of leukemia
o Sodium depletion, dehydration, diuretic
use
o Suicidal or impulsive patients
o Febrile states
 AE:
o Serum levels < 1.5 mEq/L: CNS problems
(lethargy, skurred speech, muscle
weakness, fine tremor, polyuria, NV,
diarrhea
o Serum levels 1.5 – 2 mEq/L:
intensification of all of the above
reactions, with ECG changes
o Serum levels 2 – 2.5 mEq/L: ataxia, clonic
movements, hyperreflexia, seizures, severe
ECG changes, hypotension, large output of
dilute urine, fatalities sec to pulmonary
toxicity
o Serum levels > 2.5 mEq/L: complex multi-
organ toxicity, significant risk of death
 Drug-drug interactions:
o Lithium + haloperidol = encephalopathic
syndrome (weakness, lethargy, confusion,
tremors, extrapyramidal symptoms,
leukocytosis, irreversible brain damage
o Lithium + carbamazepine = inc CNS
toxicity
o Litihium + iodode salt = inc risk of
hypothyroidism
o Lithium + thiazide diuretic = inc risk of
lithium toxicity
o Lithium + indomethacin = higher lithium
plasma levels
CENTRAL NERVOUS SYSTEM STIMULANTS
 For attention deficit disorder and narcolepsy
 Calm hyperkinetic children and help them focus on
one activity for longer period
 Redirect and excite the arousal stimuli from the
RAS; inc stimulation of catecholamines from
presynaptic neurons, leading to inc stimulation of
postsynaptic neurons
 Methylphenidate (Ritalin, Concerta)
o For ADHD, narcolepsy
 Dexmethylphenidate (Focalin)
o Isomer of methylphenidate
o Used in lower doses
o Only for the treatment of ADHD in
patients 6 yrs and older
 Dextroamphetamine (Dexedrine)
o Short-term adjunctive therapy for
exogenous obesity (obesity caused by
overeating)
 Modafinil (Provigil)
o Newer drug for narcolepsy (Shift work
sleep disorder is a circadian rhythm sleep
disorder which affects people who change
their work or sleep schedules frequently or
work longterm on other than the day shift.
o Such recurrent interruption of sleep
patterns may result in insomnia and/or
excessive sleepiness.
o Improving wakefulness in obstructive
sleep apnea/hypopneas syndrome
(involves episodes of overly shallow
breathing or an abnormally low respiratory
rate)
o Not associated with many of the systemic
stimulatory effects of some of the other
CNS stimulants
 PK:
o Safety for use in pregnancy and lactation
not yet established
 CI:
o Marked anxiety, agitation, tension
o Sever fatigue or glaucoma
o Cardiac disease
o Pregnancy/lactation
o Caution in seizures, drug dependence,
alcoholism, hypertension
 AE:
o Nervousness, insomnia, dizziness,
headache, blurred vision, difficulty with
accommodation
o Anorexia, nausea, weight loss
o Hypertension, arrhythmia, angina
o Skin rashes
o Physical and psychological dependence
 Drug-drug interaction:
o With MAOIs = inc risk of AE and toxicity
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o With guanethidine = dec in
antihypertensive effects
o With TCAs or phenytoin = risk of inc drug
levels