Approach
Amfetamine and methamphetamine use disorders are chronic, relapsing conditions, associated with compulsive drug-seeking behaviours and drug use, and resulting in long-term negative central nervous system and functional changes. Methamphetamine has longer-lasting and more severe adverse effects on the central nervous system than amfetamine.[4] In common with all substance use disorders, diagnosis is based on clinical assessment via a combination of patient interview, collateral history, and review of available medical records.
A number of signs and symptoms in addition to laboratory tests may provide further evidence of recent or long-term substance use, or of withdrawal from use. For all patients who may have used amfetamine/methamphetamine recently, it is important that healthcare professionals recognise early warning signs of acute toxicity suggestive of cerebrovascular and cardiovascular complications, which may indicate an acute risk to life (see 'Acute toxicity: clinical assessment', below).[6]
Acute toxicity: clinical assessment
The initial assessment should include a basic assessment of vital signs, to help identify any acute problems suggestive of a need for urgent medical care.[14]
Early warning features suggestive of a need for close monitoring due to potential impending risk to life include:[6]
dyspnoea
angina
palpitations
cough and haemoptysis.
The above symptoms suggest a need for close medical observation, with consideration of early transfer to an intensive medical environment (e.g., critical care) as appropriate.[6] Other features suggestive of a need for inpatient medical admission (often in critical care) include hyperadrenergic symptoms (tachycardia, hypertension, hyperthermia, and agitation), hypertensive crisis, vasculitis, cerebral haemorrhages, and central nervous system toxicity (i.e., severe agitation, seizures).[14][24]
The acute toxicity of an overdose typically presents as exaggerated 'normal' effects of the drug. History and examination may be challenging due to agitation, paranoia, and/or psychosis.[49] Initially, there may be long periods without food or sleep. The following signs and symptoms may be present: sympathetic stimulation with hypertension, tachycardia, hyperthermia, and increased central nervous system effects including euphoria, increased energy, heightened alertness and attentiveness, insomnia, anxiety, tremors, hallucinations, psychosis (often closely resembling that seen in schizophrenia), paranoia, physically harmful behaviour towards others, tooth grinding, and increased libido.[24][49] This action phase is typically followed by a reaction or recovery phase characterised by exhaustion and fatigue, giving way to long periods of sleep and periods of extreme hunger. For more information on diagnosis and management of acute toxicity, see Amfetamine overdose.
Mental status examination
This is recommended as part of an initial comprehensive assessment, and should identify co-occurring psychiatric symptoms or conditions, including those suggestive of a need for urgent psychiatric care. Symptoms may include:[14]
Psychosis
Risk of self harm or harm to others
Mood disorder
Cognitive impairment
Attention deficit hyperactivity disorder (ADHD)
Indicators of risk of self-harm or harm to others, such as agitation or psychosis, signal the necessity for an urgent referral for comprehensive psychiatric evaluation, either voluntarily or involuntarily, depending on the individual's clinical presentation.[14]
Amfetamine and methamphetamine use disorder: history
Amfetamine and methamphetamine use disorder is a pattern of amfetamine use leading to clinically significant impairment or distress, defined by the presence of at least 2 of 11 symptoms during a 12-month period. The course of amfetamine and methamphetamine use disorders is typically characterised by repeated periods of intense use, with intermittent periods of abstinence and relapse.[1][50] People exposed to amfetamine-type substances may develop stimulant use disorder in as little as 1 week, although onset is not always this rapid.[1] In particular, smoking and intravenous use are associated with rapid progression to severe-level stimulant use disorder.[1] Tolerance occurs with repeated use. Withdrawal symptoms include hypersomnia, increased appetite, and dysphoria, and may enhance craving. Most people with stimulant use disorder have experienced tolerance or withdrawal.[1]
Consider asking patients about the context of their stimulant use.[14] Reasons may include weight loss, academic and performance enhancement, staying awake, and chemsex (intentional sex under the influence of psychoactive drugs). People who use these drugs at a younger age (e.g., adolescents) are most likely to start using amfetamine/methamphetamine for recreational and performance-enhancement purposes, such as to assist with school work or sporting performance. Those starting use at a later age (adulthood) are more likely to 'self-medicate' in response to adverse or stressful life events.[51] Female adolescents are the demographic group most likely to use amfetamine or methamphetamine for weight loss or maintenance.[52]
Asking about the following guides the risk assessment, and informs harm reduction measures:[14][49]
Amount and frequency of use, including binge use.
Route of administration, which may be inhalation, intravenous, intramuscular, or transmucosal (oral/nasal).
Use of stimulants with nobody else present.
Co-use with alcohol or other drugs (e.g., alcohol, opioids, benzodiazepines, cannabis). Co-use of methamphetamine and opioids is increasingly common, and elevates the risk of mortality. Some people use methamphetamine as an opioid substitute, to obtain a synergistic high, or to balance out the effect of opioids.[53]
History of overdose.
History of stimulant-related visits to the emergency department, and hospitalisation.
Risky sexual behaviours.
Biopsychosocial assessment is recommended, including age of onset of substance use, family history of substance-use related issues, ongoing risks related to substance use and associated behaviours, treatment history and outcomes, psychosocial functioning, and factors which may guide treatment and recovery support needs. This includes social determinants of health, such as access to safe housing, economic well-being, and transportation challenges.[14]
Amfetamine and methamphetamine use disorder: examination
Physical effects associated with long-term use may include:[24][49][54][55]
Cardiovascular dysfunction (e.g., hypertension, aortic dissection, acute coronary syndromes, pulmonary hypertension, cardiomyopathy)
Cachexia
Appearing older than chronological age
Skin lesions or infection (often from picking/scratching at the skin to remove imagined insects)
Needle marks, or cellulitis from injection sites (from intravenous use)
Nasal redness (from nasal use)
Chemical burns
Impaired dental hygiene/tooth grinding/broken teeth.
Other rare but reported effects of longer-term use include cerebral haemorrhage, vasculitis, giant gastric ulcers, and various cardiac arrhythmias.[56]
Psychological and neuropsychiatric effects associated with long-term use include:[24][49]
psychosis (sometimes persistent)
paranoia
anxiety
insomnia
neurocognitive decline
confusion
social and occupational deterioration
exposure-induced depression
excessive tiredness (anergia and fatigue)
parkinsonism
anhedonia (following withdrawal).[24]
Initial investigations
Alterations in liver, kidney, and muscle function are associated with both acute and longer-term use of amfetamine and methamphetamine.
Recommended initial tests include:[14][49]
Blood chemistries (i.e., full blood count, electrolytes, liver and kidney function tests, and muscle enzymes) to evaluate for medical complications of substance use; note that amfetamine-induced cardiac arrhythmias are associated with low potassium levels.
Urine toxicology testing or blood or urine gas chromatography/mass spectrometry (GC/MS), to inform the diagnosis for patients in whom the use of amfetamine/methamphetamine is in doubt, or to identify substance use that could produce drug-drug interactions when considering pharmacotherapy to manage stimulant intoxication or withdrawal.
12-lead ECG and cardiac blood markers, to assess for cardiac dysfunction, particularly if there is chest pain, hypertension, and/or arrhythmia.
Chest X-ray, e.g., if there is suspicion of pneumothorax or pneumonia.
An abdominal flat-plate x-ray or abdominal CT scan can be performed if body packing (concealment of drug packets in body cavities) or ingestion of drug packets is suspected. Metal wrappings such as aluminum foil make for easy radiographic identification, but it may be more challenging to radiologically determine the presence of plastic bags and condoms.
Some drugs are metabolised to amfetamines. Selegiline is metabolised to L-amfetamine and L-methamphetamine and causes a false-positive GC/MS result. Quantitative isomer analysis can distinguish the L from the R isomer. Clobenzorex, an anorectic medication from Mexico, is metabolised to D-amfetamine, giving positive screening, GC/MS confirmation, and qualitative isomer analysis.
After stabilisation, patients should be evaluated for infectious diseases if not carried out already, regardless of the route of administration of drug use, including testing for HIV, hepatitis B and C, and other STIs, as well as tuberculosis.[57] The location of testing for chlamydia and gonorrhoea is guided by all sites of exposure. Although evidence is lacking, this advice is based on expert opinion given the higher prevalence of these conditions in patients with stimulant use disorders, regardless of route of administration.[14]
Subsequent investigations
A blood toxicology screening and confirmation tests should be performed when there is need for forensic confirmation or for concentrations of specific drugs and toxic metabolites. Often performed at time of associated contact with the criminal justice system or death.
Testing for complications
An echocardiogram is recommended to evaluate for valvular lesions and pulmonary hypertension in people with a history of longer-term use of amfetamine/methamphetamine.
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