AMPHETAMINE RELATED

PSYCHIATRIC DISORDER
Pembimbing :
dr. Iwan sys Indrawanto, Sp.KJ

Didi Yudha Trisandya

201720401011161
 Methamphetamine (METH) belongs to a class of compounds called
phenethylamines which exhibits catecholaminergic, dopaminergic,
and serotonergic effects. It was first manufactured in 1893 for the
treatment of asthma and upper respiratory congestion. Today,
methamphetamines are clinically used for the treatment of short-term
obesity, narcolepsy, and attention deficit disorder with hyperactivity.
Introduction

The routes of methamphetamine administration may be inhalation,

intravenous, intramuscular, or transmucosal (oral/nasal). Peak plasma
levels can range from 5 to 10 minutes via intravenous administration,
and up to 2 to 3 hours if taken transmucosally. Symptoms typically last
hours to days, based on dosage and strength, and dissipate once the
drug is eliminated from the body.

Methamphetamines impair the cognitive thought process and

subsequently precede acute psychosis. This suggests that continued
impairment due to methamphetamine use is a precursor to psychosis.
 ETIOLOGY

Amphetamine-related psychiatric disorders are

a rare condition associated with amphetamines.
• Worldwide between 14 and 55 million people between the
ages of 15 to 64 are estimated to use amphetamines as
reported by the United Nations Office on Drugs and Crime
2015. Of these, an estimated 17 million people are
dependent on amphetamines.
• In the United States in 2008 approximately 13 million (5%)
of people 12 and older had reported using amphetamines
in their lifetime. While this number was down from 6.5%
in 2002 (NSDVH 2009), these numbers are still
extremely high and relevant to the medical community.
• In addition to this, patients who have a methamphetamine
use disorder and are entering substance abuse treatment
centers have a higher likelihood to be referred by the
criminal justice system than do patients with all other
substance use disorders combined (59% versus 38%). This
former group is also twice as likely to need long-term
treatment than patients abusing other drugs (17% versus
8%; SAMHSA 2009). Some studies have suggested about
30% of patients with methamphetamine-induced
psychosis end up with a primary psychosis over time. After
cannabis, methamphetamines are the most widely abused
illicit drug worldwide.
Pathophysiology
increase of
Inhibit Dopamine
Amphetamine dopamine concentrations
reuptake in neuronal
synapsis

Acting on the nucleus accumbens by

Interactions with Increased amounts of inducing dopamine and norepinephrine
vesicular dopamine in the acting on the nucleus accumbens by
monoamine cytosol inducing dopamine and norepinephrine
transporter 2

feeling of euphoria is
5
elicited
Pathophysiology
this dopamine-
induced reward
feedback loop is the
cause of addiction

changes in the change in cognitive This damage leads to dis-

prefrontal cortex of behavioral function
those exposed to regulation of glutamate in the
repeated which is thought to cerebral cortex, a precursor to
amphetamine usage. be a precursor to psychosis
primary psychosis

6
TOKSICOLOGY
• Amphetamines belong to a class of central nervous system (CNS)
stimulants called the phenethylamines. Amphetamines contain a
methyl group to the alpha position on its carbon chain while
methamphetamines have a second methyl group.
• This allows methamphetamine to be very lipophilic, increasing its
volume of distribution and CNS stimulation. Methamphetamine is an
indirect neurotransmitter causing increased levels of dopamine,
epinephrine, and norepinephrine in the cytosol.
TOKSICOLOGY
• Another effect of methamphetamine is blocking the neurotransmitter
reuptake transport system. These two processes lead to both alpha
and beta-adrenergic receptor stimulation causing sympathomimetic
symptoms (hypertension, tachycardia, hyperthermia,
vasoconstriction, and diaphoresis). The excess dopamine in the
cytosol leads to drug craving/seeking phenomenon and psychiatric
symptoms.
• Amphetamines are both renally and hepatically excreted, including
the cytochrome CYP2D6 pathway.
History and Physical
Acute methamphetamine usage and resultant psychosis can present
like a sympathomimetic toxidrome. Vital signs and a detailed history
are difficult to obtain secondary to agitation, intoxication, and possible
withdrawal. The diagnosis should be considered in any patient with
tachycardia, hypertension, and psychosis. If possible, the history should
focus on the route of administration, dosage (amount and the number
of usages), and over what time frame. Also, ask about co-ingestions, as
most users will use sedatives (alcohol, opioids, benzodiazepines,
cannabis) to help distinguish mixed presentations and symptoms. At all
times, protection of the patient and the medical staff need to be
considered if agitation or psychosis present.
History and Physical
Physical exam findings usually reveal a malnourished, disheveled individual
with variable mood or behavior changes.
Tachycardia, hypertension, hyperthermia, and diaphoresis are some of the
hallmark sympathomimetic symptoms are seen with methamphetamine use.
Excoriations are very common due to psychosis and “skin picking.”
Intraoral exam reveals decayed dental enamel and inflamed gingiva,
commonly called “meth mouth.” This is due to poor oral hygiene, decreased
salivation, and teeth grinding. Patients can also display choreiform
movements and are hyperstimulated with continuous pacing or other
repetitive actions. Both acute and chronic usage has been associated with
paranoid delusions, hallucinations, mood swings, homicidal or suicidal
thoughts, and psychosis.
 • Never delay treatment of suspected
methamphetamine psychosis while
EVALUATION awaiting urine or serum toxicology. False
negatives (excretions and metabolism
abnormalities) and false positives (cross-
reactivity) are not unusual and can cloud
the clinical picture and healthcare
providers’ judgment.
• Full electrolyte panel, serum lactate,
BUN/creatinine, creatinine phosphokinase,
coagulation factors, and hepatic enzymes
should all be checked.
• An electrocardiogram is helpful in the
tachycardic patient for rhythm
identification and associated ischemia. X-
ray imaging is helpful in ruling out
associated trauma, pneumothorax due to
inhalation, and aspiration or infiltrates. CT
imaging rules out more complex issues like
strokes, vascular dissections, and intra-
abdominal or intra-thoracic infections.
Treatment / Management
• Evidenced-based clinical guidelines for the treatment of methamphetamine associated
psychosis are not readily available. This is largely due to a lack of large randomized
clinical trials of pharmacologic agents used for the treatment of this disorder.
• Generally, acutely agitated psychotic patients are treated with intravenous
benzodiazepines (lorazepam, diazepam, or midazolam) as first-line agents. However, if a
second line agent is needed, antipsychotic medicines like risperidone, haloperidol, and
olanzapine have been successful in managing methamphetamine associated psychosis.
• Little is known on the efficacy and safety in children/adolescents, and extreme caution is
advised in this population because they are prone to more adverse effects of
antipsychotics than adults.
• It is important to mention that remission of psychotic symptoms usually resolves in one
week with abstinence from methamphetamines. This suggests most methamphetamine
associated psychosis resolve without pharmacologic therapy. Long-term therapy usually
relies on abstinence and cognitive behavioral therapy in combination with 12-step
programs (Alcoholics Anonymous, Narcotics Anonymous) to strengthen the patients’
support system.
Differential Diagnosis
• The key to diagnosing methamphetamine psychosis is identifying the symptoms
associated with its sympathomimetic presentation. These include tachycardia,
hypertension, mydriasis, hyperthermia, and agitation.
• A wide variety of overdoses and toxidromes have similar presentations, but there are
several key points to remember. With anticholinergic toxicity, patients have anhidrosis,
not diaphoresis.
• Also, duration of action is an important key. Other psychostimulants like cocaine (30
minutes) and PCP (less than 8 hours) do not have as long of a peak action potential as
methamphetamine (more than 20 hours). Other intoxications from serotonin or
monoamine oxidase inhibitors are much harder to distinguish, but typically do not
produce as much agitation/psychosis and also have frequent tremors of the extremities.
Heat stroke can be distinguished hopefully from history but may have varying degrees of
confusion, and either anhidrosis or diaphoresis.
• Thyrotoxicosis and pheochromocytomas can be ruled out with TSH, free T3, T4, and
plasma metanephrine or 24-hour urine catecholamines, respectively. Co-ingestion is
common, also delaying diagnosis because of mixed toxidromes. Typical drugs of abuse,
as well as, over the counter medicines can be measured with urine or serum marker
levels.
COMPLICATIONS
• Depression
• Psychosis
• Generalized anxiety
• Insomnia
• Loss of memory
• Neurological deficits
• Additional substance abuse
• Social dysfunction
OTHER ISSUES
• Never wait for toxicology results before instituting treatment in
methamphetamine-associated psychosis or methamphetamine
toxicity, as urine toxicology is susceptible to false positives and
negatives.
• Antipyretics have no role in methamphetamine-associated
hyperthermia, as this is caused by muscle activity and not changes in
the hypothalamus.
• Suspect methamphetamine-associated psychosis in all patients who
present with agitation/psychosis, with hypertension, tachycardia,
hyperthermia, and anhidrosis.
OTHER ISSUES
• Look for co-ingestions in all suspected cases of methamphetamine
associated psychosis as other drugs of abuse are common and can
cloud the clinical picture.
• Most symptoms of methamphetamine associated psychosis resolve
without pharmacotherapy in as little as one week with abstinence
and antipsychotics are not needed.
• A larger percentage of methamphetamine associated psychotic
patients go on to develop a primary psychosis in the future.
• After cannabis, methamphetamine is the most commonly abused
drug worldwide.
 • Amphetamine associated psychiatric disorder is a
Enhancing Healthcare relatively common presentation to the
emergency department. It carries a very high
Team Outcomes morbidity and mortality if not promptly
diagnosed and treated.
• The triage and the emergency room physician
must be aware of this disorder and quickly make
appropriate referrals for treatment. Because
these patients may suffer from a variety of acute
psychiatric disorders including suicidal or
homicidal thoughts, close monitoring is vital.
• In addition, the healthcare staff also require
protection and hence, it is important to work as a
team when examining the patient. The outcomes
of these patients depend on the severity of
psychiatric impairment and other comorbidities.
• For patients who abstain from the further use of
amphetamine, the prognosis is good. However,
many of these patients also have personality
disorders and often fail to comply with
treatment. Most get lost to follow up and
eventually end up with legal problems leading to
incarceration.
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