Topic 3: Stimulant Induced Psychosis Pharmacological Management

Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. The symptoms of psychosis include: lack of concentration, delusions of persecution, increased motor activity, disorganization of thoughts, lack of insight, anxiety, suspicion and auditory hallucinations.

The thought disorders that occur in schizophrenia characterized by a splitting and loosening of associations, a concreteness of abstract thought, and an impairment in goal-directed thought, may be less prominent in amphetamine induced psychosis.

Psychosis may be precipitated acutely by amphetamine due to its effects on dopaminergic activity in the CNS. In the longer term, the neurotoxic effects of the drugs on serotonin and dopamine neurons and dopamine transporters may play a role.

A meta-analysis by Lecomte T et al, 2018 estimated that 36.5% of methamphetamine users have a history of amphetamine psychosis or substance-induced psychotic disorders. Up to 25% of those initially diagnosed with drug induced psychosis after some years develop a primary psychotic disorder, and even higher figures when looking at methamphetamine induced psychosis (Caton CL et al, 2006; Kittirattanapaiboon P et al, 2010).

Having an amphetamine use disorder was associated with higher odds of psychosis (OR = 3.0, 95%CI 1.9–4.8; AOR = 2.4, 95%CI 1.6–3.5).

Arunogiri et al., 2018 reported that there is moderate evidence that the frequency of use of methamphetamine and the severity of dependence to the drug can increase the chance of developing amphetamine psychosis.

However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis.

Who is more vulnerable for stimulants induced psychosis?

The increased vulnerability for acute amphetamine induced psychosis seen among those with:

• Schizophrenia
• Schizotypal personality
• Having other psychiatric disorders
• Using other co-morbid psychoactive substance
• Individuals who previously have experienced amphetamine-induced psychosis.

The evidence about the treatment for amphetamine psychosis is very limited.

PHARMACOLOGICAL MANAGEMENT OF STIMULANT INDUCED PSYCHOSIS

The review by Dimy Fluyau et al, 2019 suggests that antipsychotics are efficacious and clinically relevant for the treatment of amphetamine psychosis. However, amphetamine psychosis may respond to any of the arsenal of antipsychotics for the treatment of primary psychotic illnesses (psychosis not induced by a drug), and the psychosis induced by amphetamine may be self-limited.

• Patient should be given oral/injectable benzodiazepines.

• However, if patient is significantly acting out. Not being managed by benzodiazepines due to any reason, then anti-psychotics can be given for acute psychotic symptoms.
• Antipsychotic medications effectively reduce symptoms of amphetamine psychosis, the newer generation and more expensive antipsychotic medication, olanzapine, demonstrates significantly better tolerability than the more affordable and commonly used medication, haloperidol (Shoptaw SJ et al, 2009). Use them in lower dosage initially.

ANTI-PSYCHOTICS

EVIDENCE

SIDE-EFFECTS

OLANZAPINE

Significant improvement from baseline to end point measured by a reduction of the Clinical Global Impression Severity Scale and Brief Psychiatric Rating Scale scores (p < 0.001) (Leelahanaj T et al, 2006).

Somnolence, headache, weight, and skin rash. Olanzapine may be a better treatment option than haloperidol in light of an inducing few or no extrapyramidal symptoms, although the medication costs substantially more than haloperidol.

ARIPIPRAZOLE

Aripiprazole seemed to have better potential than risperidone in reducing negative symptoms (Wang G. et al, 2016).

Headache, dizziness or light headedness, insomnia or drowsiness, restlessness or anxiety, 

Rarely- Suicidal thoughts or behaviours (especially in children, teenagers, and young adults), allergic reactions

RISPERIDONE

Risperidone seemed to have better potential than aripiprazole in reducing positive symptoms of amphetamine-induced psychosis (Farnia V et al, 2014).

Headache, dizziness or light headedness, insomnia or drowsiness, restlessness or anxiety, 

Rarely- Neuroleptic malignant syndrome, tardive dyskinesia

low white blood cell count

Increased risk of stroke in elderly, postural hypotension

HALOPERIDOL

Haloperidol is effective for the treatment of this psychosis (Angrist et al, 1974; Tinklenberg, 1976).

Extrapyramidal syndrome, hypertonia, dyskinesia, and hypersalivation.

Comparison of risperidone vs Aripiprazole- A randomized controlled trial by Farnia V et al, 2014, concluded risperidone to be statistically superior to aripiprazole in reducing hallucination, delusion, bizarre behavior, and thought disorder. While aripiprazole was statistically superior to risperidone at reducing poverty of speech, apathy, anhedonia, and inattentiveness (Wang G. et al, 2016).

Comparison of FGAs and SGAs- It is safer to use second generation anti-psychotics, first generation have more chances of developing extra pyramidal symptoms (EPS). Young, anti-psychotic naive, dehydrated and agitated – this is how generally these patients presents to emergency, which is also the profile posing risk for developing EPS. Hence, should be cautious in giving anti-psychotics. Give injectables anti-psychotic after an ECG and when metabolic parameters are normal.

• In addition, the use of ascorbic acid can accelerate the renal elimination of amphetamines (Beckett et al, 1965)- Drugs that acidify the urine (ascorbic acid) can increase the renal elimination of weak bases by keeping them in their charged form.

Methamphetamine is a weak base and urinary pH averages ~6.4 when uncontrolled. At this pH only ~10% (~1 mg) of the dose is excreted in the urine within 12 hours.

When the pH of the urine is alkalinized (by chronic ingestion of sodium bicarbonate), which increases the percent of drug un-ionized (uncharged) even further, only ~1% of the dose appears in the urine.

In contrast, when the urine is acidified to 4.9-5.3 pH by repetitive ingestion of ammonium chloride, ~70% of the dose is recovered in the urine. (From Beckett & Rowland, 1965).

Whether to continue anti-psychotic or can be stopped in short term?

Compliance with Compliance with antipsychotic medication by someone with schizophrenia will not prevent a relapse or worsening of psychotic symptoms if worsening of psychotic symptoms if stimulants are used. Low-dose antipsychotic treatment may be beneficial in stimulant users, to prevent sensitisation. in stimulant users, to prevent sensitisation (Curran et al, 2004).

Anti-psychotic medications demonstrate efficacy in providing short-term relief when a heavy user of amphetamines experiences psychosis, there is no evidence to guide decisions regarding long-term clinical care using these medications for preventing relapse to psychosis (Shoptaw SJ et al, 2009).