Drug Induced Psychosis

EtOH
Cocaine
THC

ETOH INDUCED
PSYCHOSIS

EtOH induced psychosis

secondary psychosis; most often in
alcoholics
manifests as prominent hallucinations
and delusions
Causes:
acute intoxication (idiosyncratic reaction)
Withdrawal
WK syndrome

 Alcohol-related psychosis vs primary

psychotic disorders:
Alcohol-related psychosis spontaneously
clears with discontinuation of alcohol usemay resume during repeated alcohol
exposure.
alcohol-induced psychosis shows later onset
of psychosis, higher levels of depressive and
anxiety symptoms, fewer negative and
disorganized symptoms, better insight and
judgment, and less functional impairment.

EtOH Clinical presentation

Rule out psychiatric behaviour prior

Substance abuse (any other)
Fhx: psychiatric disorders
Alcohol hx:
currently intoxicated?
When was the patient's last drink?
How long has the patient been drinking during the most recent
episode?
Is the patient in withdrawal?
Did the patient fall unconscious?
Is the psychosis manifesting as visual, auditory, and/or tactile
hallucinations?
When did the patient first start to drink?
How often /much does the patient drink?
Has the patient ever gone through withdrawal/any withdrawal
seizures/DT?

Alcohol withdrawal
syndrome
Clinical syndrome that occurs when
people who are physically dependent
upon alcohol stop drinking or reduce
their alcohol consumption.

Pathophysiology of AWS
Withdrawal concept:
The body, when exposed to any type of substance attempts to
maintain homeostasis.
When exposed, it produces counter-regulatory mechanisms and
processes that attempt to keep the body in balance.
When the substance is removed, the residual counter-regulatory
mechanisms produce unopposed effects and withdrawal
symptoms.

Tolerance concept: long-term use of a substance produces

adaptive changes so that increasing amounts of the
substance are needed to produce an effect.
Ethanol affects GABA (increases inhibitory effect), NMDA
(decreases stimulatory effect) and opiod receptors.

Pathophys of EtOH
GABA stimulation
EtOH binds(activates) to postsynaptic GABAAreceptors (inhibitory
neurons) enhances effects of GABA.
In response, Cl channels openCl influxhyperpolarizes celldecreased
firing rate of neuronssedation (disinhibition occurs before).
Long-term use of ethanol subsequently results in downregulation of
GABAAreceptors (tolerance).
Chronic suppression of excitatory neurotransmission
(alcoholic)increased synthesis of excitatory neurotransmitters (NE,
serotonin, dopamine) to attempt to maintain homeostasis.
No alcohol/decrease amt excitatory neurotransmitters (now plenty) act
without GABA inhibition to counteract withdrawal symptoms (until body
able to achieve homeostasis again).

Pathophys of EtOH
NMDA inhibition
Ethanol inhibits excitatory neurons: decreases activity ofNMDA
receptors.
Long-term use results in upregulation of NMDA receptors
(adaptation that causes tolerance).
No alcohol/decrease amt excess excitatory NMDA receptors kick
inwithdrawal symptoms
Opiod inhibition
Ethanol inhibits opioid binding to a type of opioid receptors (opiod
regulates dopamine release in some parts of brain; dopamine
produces alcohol craving) upregulation of opioid receptors.
use of opioid antagonists help prevent craving.

Alcohol idiosyncratic intoxication

and WK syndrome
Alcohol idiosyncratic intoxication:
a small amt of alcohol produces intoxication in aggression,
impaired consciousness, prolonged sleep, transient
hallucinations, illusions, and delusions.
episodes occur rapidly, can last from only a few minutes to
hours, and are followed by amnesia.
often occurs in elderly persons and those with impaired
impulse control.
WK syndrome
Thiamine deficiency leading to triad of acute mental confusion, ataxia,
and ophthalmoplegia (wernicke encephalopathy).
Korsakoff amnestic syndrome/Korsakoff psychosis : memory loss and
confabulation (memory and learning are affected out of proportion to
other cognitive functions in an otherwise alert and responsive patient)

EtOH withdrawal
presentation

Alcohol withdrawal syndrome is divided into 4 categories:

Mild withdrawal
Moderate withdrawal
Withdrawal seizures
Alcoholic hallucinosis
Delirium tremens (DTs)

Mild withdrawal (withdrawal tremulousness)

occurs within 6-24 hours following the patients last drink
characterized by tremor, anxiety, nausea, vomiting, and insomnia.

Moderate withdrawal (hallucinations)

Moderate withdrawal usually occurs 24-36 hours after the cessation of alcohol
intake and includes intense anxiety, tremors, insomnia, and excessive
adrenergic symptoms.
visual and auditory hallucinations, whole body tremor, vomiting, diaphoresis,
and hypertension.

EtOH withdrawal
presentation
Withdrawal seizures
(rum fits)
occur within 6-48 hours of alcohol cessation
Often first sign of alcohol withdrawal
Motor seizures-GTC, brief, can be multiple but usually stops
within 6 hrs spontaneously; status epilepticus rare (non-epileptic,
normal EEGs;)
If seizures partial, prolonged, long postitcal stateinvestigate
further.
Check for head trauma, stimulant drug use (cocaine,
meth./withdrawal from sedatives)
Significant amt progress to DTs; incr rate of epilepsy

Alcoholic hallucinosis
Occurs in some patients with a prolonged history of
alcohol abuse (as many as 25%)
Alcoholic hallucinosis can occur 24 hours after the last
drink and continues for about 24 hours.
Symptoms consist of persecutory, auditory, or (most
commonly) visual and tactile hallucinations
Patient's sensorium is otherwise clear.
In the early stage, the patient recognizes frank
hallucinations.
However, in the advanced stage, these hallucinations are
perceived as real and may provoke extreme fear and anxiety.
The patient can be seen pulling at imaginary objects,
clothing, and sheets, for example.
Hallucinosis is not necessarily followed by DT.

EtOH withdrawal
Delirium tremens presentation
most severe manifestation of alcohol withdrawal.
occurs 3-10 days (>48hrs) following last drink.
includes all early and intermediate symptoms of alcohol withdrawal
but with the additional feature of a profoundly altered sensorium
(disorientation, agitation, and hallucination).
DT may present without preceding seizures.
Clinical manifestations:
agitation, global confusion, disorientation, hallucinations, fever,
hypertension, diaphoresis, and autonomic hyperactivity (tachycardia and
hypertension).
Profound global confusion is the hallmark of delirium tremens. Severe
autonomic derangements are common.

Medical DDX to consider

Acute Liver Failure
Hepatic Encephalopathy
Alcoholic Ketoacidosis (starvation and
dehydationketone metabolism)
Hypertensive Encephalopathy
Uremic Encephalopathy (CRF)
Head Trauma
Meningitis
Hypoglycemia
Diabetic Ketoacidosis

Workup of EtOH withdrawal

CBC (anemia, infection)

Electrolytes (including HCO3, Mg, P)
Blood urea nitrogen (BUN), Cr
LFTs (inclusing albumin; INR if possible)
CPK (Some patients develop rhabdomyolysis)
Urine Ketones
Serum ethanol concentration
RBS
Urine/serum drug screen

CT if suspect trauma; CXR (Invx for pneumonia)

Mgt of EtOH withdrawal

calm, quiet, well-lit environment

Airway protection (turn on L L Decubitus); NPO; restraints
F+E correction (IVF with dextrose)
Thiamine (MV and Folate not help in acute setting)-prevent wernicke
encephalopathy
BZs (Phenytoin is not effective in preventing or treating alcohol withdrawal
seizures): valium, lorazepam, chlordiazepoxide (librium)
Haldol can be given once BZ given (mgt of aggression/hallucinations).
Antipsychotics may lower seizure threshold. May consider adding
antiseizure medications (eg, valproic acid/or carbamazepine) plus cogentin.
sympatholytic drug (ie, clonidine, beta-blocker) only if adequate doses of
BZ given
Note: pt may resort to using alcohol containing substances to combat withdrawal:
isopropyl alcohol, cough syrup, hand sanitizer, mouthwash, methanol, and ethylene
glycol.

Final Thoughts: mgt of alcohol related psychosis

If psychosis persists beyond elimination of alcohol an
atypical antipsychotic drug (eg, risperidone, olanzapine,
quetiapine).
No single atypical antipsychotic drug has been proven most
beneficial for treatment of persistent alcohol-related
psychosis.
Of all psychosis cases, 10-20% tend to become permanent.
Symptoms of any accompanying Korsakoff syndrome
(amnestic disorder) are highly resistant to treatment
A patient who is highly motivated to participate in an
abstinence program may benefit from the use of disulfiram.
Naltrexone is an agent helpful in decreasing the craving for
alcohol.

COCAINE INDUCED
PSYCHOSIS

 routes of administration:
inhaling (snorting)
subcutaneous injection (skin popping)
intravenous injection (shooting-up)
smoking (freebasing or smoking crack).
Rarely ingested (poor absorption and significant first-pass metabolism)

Cocaine HCL (powder form, snorted, slower, less intense high)

Crack = powder cocaine + water and backing soda (smoking
form)..lowers temperature needed to make cocaine vapourised.
Economical, rapid effect (via lungs>blood>brain)
Blocks Na channels in neurones local anesthetic effect
In heart Na blockadearrhythmia (prolongation of the QRS complex)
plus coronary artery spasm (+/- platelet activation with tachycardia
and htn)MI
Blockade of catecholamine reuptake (NE, dopamine, serotonin) in both
CNS and PNSsympathomimetic syndrome [tachycardia, hypertension,
tachypnea, mydriasis, diaphoresis, agitation]. Inhibition of dopamine
reuptake in CNS synapseseuphoria]

Medical Complications

Rhabdomyolysis
Acute coronary syndrome
Cerebral vascular accidents
Acute renal failure
Seizures
Hyperthermia
Pneumothorax
Pneumomediastinum
Pulmonary infarct
Pulmonary edema

Spectrum of cocaine effect

Intoxication>withdrawal>intoxication
with delirium >psychotic disorder
with delusion> psychotic disorder
with hallucination>mood
disorder>anxiety disorder>sexual
dysfunction>sleep disorder

Cocaine intoxication

Euphoria
Hypervigilance
Talkativeness
Grandiosity
Anxiety
impaired judgment
anger/tension
changes in sociability/changes in occupational functioning.
increase the risk for violent and even homicidal behavior.
Tachycardia or bradycardia
Mydriasis
Blood pressure change
Perspiration
Nausea or vomiting
Weight loss
Psychomotor agitation or retardation
Weakness, respiratory depression, chest pain, or dysrhythmia
Mental status examination may show a patient who is agitated and restless with a labile
affect, irritable or anxious mood, poor judgment, and impaired attention. Assess for
homicidal ideation and be aware of increased risk of violence.

Cocaine-induced psychotic disorders with delusions

Excess psychotic symptoms with delusions (within a mth of use)

Delusions can be any type: typically paranoid and/or grandiose.

Strongly held delusions despite evidence to the contrary. For

example, a female abusing cocaine may demonstrate delusions of
grandeur and believe that she possesses great wealth, intellect,
and power, despite the fact that she is a junkie.

Suicidal or homicidal ideation can occur

distortion of their mental capacity, communication, interactions

with others, ability to recognize reality, and affective response.
Unable to cope with the ordinary demands of everyday life.

MSE: guarded, tense, fearful or anxious. May or may not reveal

their paranoid delusions and may be suspicious of questions

Cocaine-induced psychotic disorders with hallucinations

Excess psychotic symptoms with

delusions (within a mth of use)
Auditory and tactile most frequent. Can
have suicidal or homicidal ideation
MSE: distracted by internal stimuli;
thought blocking (verbal outflow is
stopped mid thought by internal stimuli),
and has a reactive affect and labile mood
influenced by internal voices.

 BZsDOC for acute cocaine intoxication. Rx

complications appropriately (in addition to BZs).
BP control: BZs + phentolamine/na
nitroprusside/labetalol. Never use beta-blockers
alone (because of the unopposed alpha-agonist
activity).
Most symptoms are transient. Antipsychotics (e.g.
haldol) are advocated to treat persistent psychotic
disorders (esp when pose danger to self/others).
Newer antipsychotics (eg, risperidone, olanzapine,
quetiapine) are used for long-term management.

CANNABIS

 Marijuana has tetrahydrocannanbinol (THC) as

well as other cannanboid substances that interact
with cannanbinoid receptors in brain and immune
cells.
Effects:
Heightened mood and euphoria
Enhanced effect of food and aroma
Increased sensuality/libido; creativity;
abstract/philosophical thinking
Relaxation
Increased appetite, palpitations with hypotension
Red eyes (due to vasodilation of vessels in
conjunctiva)
decrease in short-term memory, dry mouth,
impaired motor skills
feelings of paranoia or anxiety

 Cannabis intoxication can lead to acute psychosis in

many individuals. Usually lasts within hrs and
abates.
In addition also causes symptoms of
depersonalization, fear of dying, irrational panic, and
paranoid ideas, which coincide with acute
intoxication and remitted quickly.
Short-term exacerbations of pre-existing psychotic
diseases.

one survey, it was reported that 15 percent of

cannabis users identified psychotic-like symptoms,
the most common being hearing voices or having
unwarranted feelings of persecution.

 Theory 1: cannabis use causes psychotic symptoms

in an otherwise healthy individual that would not
have occurred with abstinence.
Theory 2: cannabis use may precipitate psychosis in
individuals who are predisposed to acquiring a
psychotic disorder.
Long half life: 3-10 days after and upto mths in heavy
users still detectable in blood. Has to be factored in
when determining if pt has a non cannabis induced
psychotic disorder.

 Denmark study of pts treated for cannabis induced psychosis

with no prior hx of psychiatric illnesses. Five yr database with 3
yr follow up
535 patients vs 2721 in control gp (first time referrals for schizo
type disorders)
Cannabis gp: Younger age of onset of symptoms (27 vs 33);
more males (80+% vs 57)
44.5% later developed a schizophrenia-spectrum disorder.
Paranoid schizophrenia was most common (more than half)
Time to dx: 1 yr from cannabis induced symptoms for nearly
half. In 17% it took upto 3 yrs.
No mention if pts were off cannabis when disorders were dx but
assume so.

References
http://
emedicine.medscape.com/article/81950
2-clinical#showall
http://
emedicine.medscape.com/article/28984
8-clinical#showall
http://
emedicine.medscape.com/article/2901
95-overview
Cannabis-Induced Bipolar Disorder
with Psychotic Features: A Case